Breakthroughs in Stroke, Brain Cancer, and Tissue Engineering

We may dream of discovering a "fountain of youth," a magic bullet treatment to achieve immortality with just a single elixir, fruit, capsule, or injection. But the modern reality of the anti-aging effort is that, for now, we must attack each killer disease individually.

An impressive new treatment for cerebrovascular accidents -- brain strokes -- was developed at the University of Manchester.

Researchers induced a stroke in the rats and the drug IL-1Ra, or a placebo for comparison, was injected under the skin. The researchers did not know which animals had been given which drug. This is a similar process to what happens in clinical trials of medicines.

The results were startling. MRI scans revealed that the rats that were given IL-1Ra up to three hours after the stroke had only about half the brain damage of the placebo group.

Professor Rothwell said: “This is the first time that we are aware of a potential new treatment for stroke being tested in animals with the same sort of diseases and risk factors that most patients have. The results are very promising and we hope to undertake further clinical studies in stroke patients soon.”

IL-1Ra works by blocking the naturally occurring protein interleukin 1. Researchers at The University of Manchester have identified that it is a key cause of brain injury following a stroke.

Interleukin 1 encourages inflammation in the area of the brain affected by stroke. This sends out signals to attract white blood cells and to switch on microglia cells in the brain. Because the barrier surrounding the brain has been weakened by the stroke the white blood cells find it easier to enter the brain. But instead of helping the inflamed area they actually kill nerve cells and worsen the injury. The increasing presence of these cells also explains why the damage in the brain gets worse over time following a stroke.

IL-1Ra also reduces the amount of damage to the blood-brain barrier following a stroke so the harmful cells can’t enter the brain. In the recent experiments IL-1Ra reduced the damage to the blood-brain barrier by 55% in healthy rats and 45% in rats with underlying health conditions. In all types of rats the drug reduced the amount of activated microglia cells by 40% compared to the placebo group. _Manchester

A similar type of anti-inflammatory therapy is also being developed to combat Alzheimer's, multiple sclerosis, traumatic brain injury, and other forms of neurodegenerative and inflammatory brain disease.

The fight against brain cancer and other solid tumours was advanced recently by the University of Tennessee Space Institute. The technique utilises a femtosecond laser to both precisely target and destroy tumours.

“Using ultra-short light pulses gives us the ability to focus in a well confined region and the ability for intense radiation,” said Parigger. “This allows us to come in and leave a specific area quickly so we can diagnose and attack tumorous cells fast.”

Once the cancerous area is precisely targeted, only the intensity of the laser radiation needs to be turned up in order to irradiate, or burn off, the tumor. This method has the potential to be more exact than current methods and to be done as an outpatient procedure replacing intensive surgery.

“Because the femtosecond laser radiation can be precisely focused both spatially and temporally, one can avoid heating up too many other things that you do not want heated,” said Parigger. “Using longer laser-light pulses is similar to leaving a light bulb on, which gets warm and can damage healthy tissue.”

The technology can be especially helpful to brain cancer victims. The imaging mechanism can non-invasively permeate thin layers of bone, such as the skull, and can help define a targeted treatment strategy for persistent cancer. The method also overcomes limitations posed by current treatments in which radiation may damage portions of healthy brain tissue. It also may overcome limitations of photodynamic therapy that has restricted acceptance and surgery that may not be an option if not all carcinogenic tissue can be removed. _UTSI

Combining the targeting function with the therapeutic heating function saves time and improves therapeutic precision, and the improved precision of targeting saves surrounding normal tissue.

Research engineers at the University of Toronto have developed a new, rapid method of tissue engineering, capable of creating 3-D layered tissues in an advanced hydrogel.

Scientists manipulate biomaterials into the micro-device through several channels. The biomaterials are then mixed, causing a chemical reaction that forms a "mosaic hydrogel"—a sheet-like substance compatible with the growth of cells into living tissues, into which different types of cells can be seeded in very precise and controlled placements.

Unique to this new approach to tissue engineering, however, and unlike more typical methods for tissue engineering (for instance, scaffolding, the seeding of cells onto an artificial structure capable of supporting three-dimensional tissue formation) cells planted onto the mosaic hydrogel sheets are precisely incorporated into the mosaic hydrogel sheet just at the time it's being created—generating the perfect conditions for cells to grow. _UToronto

This approach is likely to evolve rapidly to provide quick replacement tissues of a simpler nature, such as skin grafts. More complex tissues and organs will require sophisticated scaffolds, to allow the tissue to maintain shape and resist a variety of physical forces likely to come to bear in a variety of implant locations.

The fight against deadly diseases and ageing itself, must necessarily take on multiple forms. Humans have not, after all, conquered even the most rudimentary of enemies -- the virus. Despite our best efforts, we are still vulnerable to new outbreaks of emerging infectious diseases. And we will always be vulnerable to chance events such as accidents -- both terrestrial and cosmic.

But it is in the nature of our slightly advanced monkey selves to pursue our continued existence, as long as we can. h/t Brian Wang

Progress in Regenerative Medicine: Anthony Atala at Wake Forest University

[Anthony] Atala currently heads up more than 300 researchers in the Wake Forest University lab who are working on growing more than 30 different organs and body tissues.

In one trial for the U.S. Armed Forces, his team is collecting healthy skin cells from injured soldiers, processing them, and then spraying them onto battle wounds as a tailored treatment for healing. For deeper wounds, they are in the process of developing an ink jet printer that scans a wound and creates a custom map of the defect.

"After the scan, the printer can go back and print multiple layers of cells right over the wound," Atala said.

The idea of using a patient's own cells rather than relying on those of a donor is important because it eliminates the need to find a "match." For any transplant procedure there is a concern that tissues from a donor will be rejected by a recipient's body. _ABC_via_NBF

There are many challenges to creating lab-grown replacements for human organs. But the promise of being able to create a perfect tissue match replacement organ, and no longer being forced to wait at the bag of the organ donour line, is simply too great a promise to ignore.

Regenerative Medicine and Organ Transplantation

By the early 1990s, tissue engineering had become an established field of investigation (30). Concurrently, adult stem cells and ESC were isolated in animals (31, 32) and humans (33), and the advent of nuclear transfer technology made animal cloning possible (7, 34–36). These apparently distinct fields of science had one unifying concept, namely the regeneration of living and functioning body parts destined to replace diseased or damaged cells, tissues, or organs (7). In 1999, the term “regenerative medicine” was coined to describe the use of natural human substances, such as genes, proteins, cells, and biomaterials to regenerate diseased or damaged human tissue (4, 7). It is important to note that the terms tissue engineering and regenerative medicine are not synonymous. The term regenerative medicine is used to define a field in the health sciences that aims to replace or regenerate human cells, tissues, or organs to restore or establish normal function (37). The process of regenerating body parts can occur in vivo or ex vivo and may require cells, natural or artificial scaffolding materials, growth factors, or combinations of all three elements. In contrast, the term tissue engineering is narrower in scope and strictly defined as manufacturing body parts ex vivo, by seeding cells on or into a supporting scaffold. _Excerpted from: Regenerative Medicine and Organ Transplantation: Past, Present, and Future (Atala et al)

Since the early days of tissue engineering, advances in stem cell science, genetic engineering, tissue engineering, 3D printing, and related fields, have given the field of regenerative medicine new powers that were not previously imagined. While all of those sciences continue to advance, it remains for the regenerative medicine specialist to bring them all together and create a new state of the art in tissue and organ transplantation.

Transplantation 2011: Regenerative Medicine and Organ Transplantation

One useful "shortcut" in creating new organs from a patient's own tissues, is the use of "acellular" scaffoldings. A donour organ is stripped of its cells, leaving only the supporting acellular matrix scaffolding, including vascular matrix. This scaffolding is then seeded with replacement cells and growth factors for the tissue being replaced, ie vascular, renal, hepatic etc.

Hepatology: Whole Organ Acellular Scaffolds

A significant advancement in the field of bioscaffold design has been the utilization of decellularized tissue as the three-dimensional scaffold in tissue engineering strategies.11 Our laboratory has previously reported the successful decellularization of porcine aortas and urinary bladder submucosa for use as scaffolds for cell seeding.2, 12 These decellularized aortas were seeded with endothelial progenitor cells and implanted into sheep, and the neovessels remained patent for more than 4 months.2 However, effective decellularization of thicker organs and tissues has been very difficult to achieve due to inefficient penetration of the decellularization solution into the organ. More recently, Ott et al. have developed a more effective method for organ decellularization.13 They have shown that by perfusing a detergent solution through the vascular network rather than relying on agitation and diffusion alone, the entire mouse heart could be decellularized and used as a scaffold for tissue engineering. However, cell seeding of three-dimensional, naturally derived scaffolds presents additional challenges.14 For example, to achieve a recellularized human liver adequate for clinical use, one needs to transfer approximately 10 × 1010 liver cells into the scaffold. So far, such a task has not been successfully achieved. Although perfusion bioreactors have been developed to address cell seeding problems,15, 16 cell seeding across the entire thickness of the scaffold has been limited due to the lack of intrascaffold channels.

The goal of our study was to develop a novel scaffold that human liver cells could readily enter in order to repopulate the scaffold volume. We report the production of such a scaffold via a decellularization process that preserves the macrovascular skeleton of the entire liver while removing the cellular components. The intact vascular tree is accessible through one central inlet, which branches into a capillary-like network and then reunites into one central outlet. Human fetal liver and endothelial cells were perfused through the vasculature and were able to repopulate areas throughout the scaffold by engrafting into their putative natural locations in the liver. These cells displayed typical endothelial, hepatic and biliary epithelial markers, thus creating a liver-like tissue in vitro. This technology may provide important tools for the creation of a fully functional bioengineered liver that can be used as an alternative for donor liver transplantation. _Hepatology 2011 (Atala et al)

Ideally, one would wish to grow and/or print the entire organ in the lab, but the intricate 3D complexity of the intercellular scaffolding of many organs makes such a task very difficult at this time.


ABC News Video


Wake Forest video via _PSFK.com

H/T NextBigFuture

Intravenous Stem Cells: Where Do They Go? What Do They Do?

We usually think of stem cell therapy in terms of replacing damaged cells or tissues with stem cells, which can differentiate and become the type of cell or tissue which is being replaced. But there is more to it than that, particularly in the case of intravenous stem cell infusion.

Researchers have tracked the migration of stem cells administered intravenously following an injury. At first the majority of the cells lodge within the lung, where they appear to interact with pulmonary macrophages altering the type of cell signaling molecules those macrophages release into the blood. Next the stem cells migrate to the organs of the reticuloendothelial system which includes the spleen. Surprisingly, less than 3% of infused stem cells migrate into brain tissue. So the immunomodulatory effect does not require the majority of infused stem cells to interact directly with injured brain tissue. _SciAm

It turns out that much of the beneficial effect from the intravenous infusion of stem cells comes from their effect on the immune system. IV infused stem cells apparently shift the immune system's response to injury and rejuvenation, creating a more favourable environment for healing and regeneration.

This allows the few stems cells which make it all the way to the damaged tissue, to promote regeneration locally without a harmful immune response.

Immunomodulatory stem cell studies attempt to adjust the immune response in a way that minimizes the damage associated with the initial injury, and then allows the individual’s native repair machinery to function optimally.

With even mild injury, the immune system is activated. Macrophages are a type of immune cell which participate in the post-injury immune response. With “classic” macrophage activation, the immune response is aggressively induced. Classically activated macrophages are described as having an “M1” phenotype. In the nervous system, the M1 immune response can increase the severity of an injury. Alternatively activated or “M2” macrophages, are associated with a less destructive pattern of immune system activation. This alternate/M2 response results in less immune mediated post-injury damage, as well as the possible disinhibition of native nervous system repair.

Following traumatic brain injury (TBI) children experience a loss of 12-15% of their brain tissue in the 12 months following their injury (Levin). In a study where we treated TBI children with their own bone marrow stem cells, there was minimal post injury brain volume loss in the year after TBI (Cox). In animal models of TBI, animals that experienced injury were found to have M1 macrophages throughout their injured brain tissue.

Animals treated with stem cells after TBI were found to have M2 macrophages in their brain parenchyma. Interestingly, if an animal’s spleen was removed before stem cell infusion, the benefit of the stem cell treatment was eliminated. Somehow stem cell infusion causes a change in the pattern of macrophage activation from M1 to M2, which results in a less aggressive immune response and less post-injury brain tissue death. This effect requires an intact spleen. _SciAm

So you see that in an optimal response to stem cell infusion following an injury, the patient will experience both immunomodulatory effect and a regenerative effect from the IV stem cell infusion.

When the stem cells being infused are of a broad-spectrum nature -- such as cord blood, embryonic stem cells, or pluripotent adult stem cells -- the door is wide open for other effects beyond the immunomodulatory and the regenerative (replacement) effects. It should be clear that other rejuvenative effects are also possible from broad spectrum stem cell infusion. It will simply require a good deal of research and consideration before most of those effects can be discovered and decoded for optimal therapies in the future.

Tissue Repair Gel Scaffold: Hope for Healing Cardio-Infarction

UCSD scientists have developed an injectable gel to reinvigorate damaged heart tissue, after a heart attack. Heart failure subsequent to myocardial infarction is a significant cause of death in adults of advanced nations. Tissue replacement and revitalisation treatments such as this, promise to add healthy years to the lives of tens of millions of people, worldwide.

Researchers claim to have developed a new injectable hydrogel which they say could be used to repair tissue damaged by heart attacks.

A team at the University of California, led by Karen Christman, hopes to bring the gel to clinical trials within the next year, the latest edition of Journal of the American College of Cardiology reported.

Therapies like the hydrogel would be a welcome development, Christman explained, since there are an estimated 785,000 new heart attack cases in the US each year, with no established treatment for repairing the resulting damage to cardiac tissue.

The hydrogel is made from cardiac connective tissue that is stripped of heart muscle cells through a cleansing process, freeze-dried and milled into powder form, and then liquefied into a fluid that can be easily injected into the heart.

Once it hits body temperature, the liquid turns into a semi-solid, porous gel that encourages cells to repopulate areas of damaged cardiac tissue and to preserve heart function, according to Christman.

The hydrogel forms a scaffold to repair the tissue and possibly provides biochemical signals that prevent further deterioration in the surrounding tissues. _HinduBusinessLine

Study abstract
Abstract of earlier study

This type of cellular replacement and tissue replacement is important if we are to be able to stretch out the useful lifetimes of genetically flawed bodies. Prevention of disease is better than treatment. Genetic re-design to reduce vulnerabilities may be best of all. Stay tuned.

Previously published on Al Fin blog

We are on the road to re-growth of damaged tissues and entire organs. Development of the proper type of scaffold for organ and tissue growth is crucial.

3 Dimensional Bio-Cell Printing: Future Tissue & Organ Replacements

An optimized 3D inkjet printing process is demonstrated for structuring alginate into a tissue-like microvasculature capable of supporting physiological flow rates. Optimizing the reaction at the single-droplet level enables wet hydrogel droplets to be stacked, thus overcoming their natural tendancy to spread and coalesce. Live cells can be patterned using this process and it can be extended to a range of other hydrogels. _Advanced Materials

The dream is to be able to rapidly grow replacement tissues and organs, to allow for easy autologous replacement for a wide range of clinical reasons and circumstances -- including life extension regenerative treatments.

...Thus, it would take just under 2 hours to print a 1 cm thick tissue precursor graft and just over 5 h 30 to print a 3 cm thick kidney precursor. _Advanced Materials PDF

Swiss scientists are using a special inkjet printer to assemble three dimensional living constructs that resemble living tissues. They are still in the early stages of the research, but are achieving some interesting results.

They are working on a technique that should eventually allow them to “print” living constructs resembling human tissues in which cells can develop and interact in a coordinated and physiological manner. Their research results have recently been published in the scientific journal Advanced Materials.

“We have not yet created tissue, strictly speaking,” explains Professor Jürgen Brügger, head of EPFL’s Microsystems 1 Laboratory. “At this stage, we have essentially studied a way in which to structure biological materials in three dimensions; this research will improve cell culture and then will eventually be used as a base for creating tissues.”

...To make up a coherent whole, the cells need an environment that provides the right kinds of signals that induce very specific behavior in each of the cells – proliferation, migration, differentiation or death. In natural tissues, these signals come from molecules that make up a complex extracellular matrix (ECM). By studying the connections and communications taking place between cells and between cells and ECM molecules, the scientists were able to reconstruct this matrix and thus create a new kind of biological ink.

On a technical level, the researchers from EPFL’s two Microsystems Laboratories – under the leadership of professors Jürgen Brugger and Philippe Renaud – focused on developing a gel that could be used as a base from which the tissue could be constructed, as well as a strategy for printing droplets.

...Even though it will still be quite some time before tissue can be constructed, this technology could lead to very promising applications on the medium term. “ An exiting avenue would be to develop 3D constructs that function like human tissues and could be used as models for testing new drugs,” says Lutolf. “This is not only very interesting in a biological sense, but could also reduce the need for animal testing.” _Physorg

Learning to create life-like 3 dimensional cell cultures for research, and learning to create 3-D lab-made living tissues for replacement, are not quite the same things. But the two lines of research are likely to borrow from and contribute to each other, extensively.

This research used fibroblasts. Future research is likely to use a variety of stem cells and other precursor cells for various cell types.

Non-fluorescent NIH 3T3 fibroblasts were used in this printing as to be compatible with the fluorescent Live-Dead assay. The cells were suspended in culture medium supplemented with 0.8% wt. non-fluorescent alginate at a concentration of 1x10 6 mL -1 . Cells were inkjet printed onto 2% wt. gelatin substrates prepared with 0.9% wt. NaCl and 10 mM CaCl2, prepared in a 96-well plate. All cells were incubated for 4h before Live-Dead staining. _Advanced Materials

Rejuvenating 100 Year Old Cells: Advances in Regenerative Medicine

"Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity," explains Jean-Marc Lemaitre who directs the Inserm AVENIR team....The age of cells is definitely not a reprogramming barrier. _SD

Cell Rejuvenation via IPSC
Scientists at the Functional Genomics Institute have taken cells donated by persons older than 100 years, and reprogrammed these senescent cells into pluripotent stem cells and embryonic stem cells. These stem cells can then be differentiated into specialised cells for cell, tissue, and organ replacement therapy -- once the details are worked out.

The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.


To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific "cocktail" of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of "young" cells, both from the perspective of their proliferative capacity and their cellular metabolisms.


Researchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier.


Using this new "cocktail" of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.
In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the "rejuvenated" characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).


...The results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. "Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier." He concluded. "This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients." adds the researcher.


...Inserm's AVENIR "Genomic plasticity and aging" team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011 _SD

The first use of this new regenerative technology is likely to be cell replacement therapy. But as the methods for growing replacement tissues and organs in the lab are perfected, the methods should be suitable for producing cells to use in growing replacement tissues and organs for purposes of disease treatment and for treating senescence.

Cross-posted from Al Fin

IPS Stem Cells Are Looking More Promising for Regenerative Medicine

George Church is a professor of genetics at Harvard Medical School. He is becoming more and more deeply involved in the field of regenerative medicine, using induced pluripotent stem cells (IPS). Church was interviewed recently on how he sees the field of IPS regenerative medicine progressing.

A pioneer in developing DNA sequencing technologies, and in researching everything from epigenetics and microbiomics to synthetic biology, Church has co-founded or advises over 20 companies. He also has launched the Personalized Genome Project with a goal of sequencing the complete genomes of 100,000 volunteers.

When I asked Church what he was most excited about right now, he answered without hesitation: "I'm thinking a lot about using regeneration as the key to treatments and keeping people healthy."

TR: You mean regeneration using stem cells?

Church: Yes, induced pluripotent stem (IPS) cells (see, "Growing Heart Cells Just for You"). This is where I'm putting almost all of my chips these days, because it combines many of my interests--genomics, sequencing, epigenetics, synthetic biology, stem cells. I don't think people have fully appreciated how quickly adult stem cells and sequencing and synthetic biology have progressed. They have progressed by orders of magnitude since we got IPS. Before that, they basically weren't working.

Is this because IPS cells are relatively easy to create and to engineer?

You can use them to reprogram genomes--not sequence them, but to reprogram them genetically and epigenetically. In other words you make the minimum changes it takes to get them where you want them to be genetically and epigenetically and then you program the cells into tissues.

What do you mean?

Let's use stem cells in bone marrow as an example. They are easy to use and to get to work when you implant them in bone marrow. You might one day have three choices. You can have bone marrow from someone else that is matched to you, or that is from you, or bone marrow that is matched to you and comes to you, but is better than you. This better bone marrow might be [engineered to be] resistant to one virus, or to all viruses. It could have a bunch of alleles that you picked out of super centenarians, alleles that you have reason to believe are at least harmless and possibly helpful. So now you have choice, a patient who can take a good bone marrow that he might reject and you'll be on immunosuppressants your whole life. Or you might use your own, or your own that might fix the cancer, or your own enhanced bone marrow. And you will be able to do that for almost every stem cell population. Some of them are a little bit harder to replace, though.

Does IPS really work to accomplish this regeneration?

We have good evidence that you can create an entire mouse from IPS cells.

Has this been done?

This has been done. They have used IPS cells to grow a mouse, and they made IPS cells from that mouse. They're totipotent [able to make an entire organism], not merely pluripotent. We haven't done this for humans for obvious ethical reasons, but we will do it. As far as I know the mice have done fine.

But haven't there been some problems with mutations occurring with IPS-generated tissue?

We have a recent paper in Nature that shows that when you make human induced pluripotent stem cells you actually do get mutations in coding regions at a slightly elevated level. But I think this is temporary. We're going to use this information as an assay to make the process work better, to correct problems. You will be able to use this to improve the quality of gene therapy because that's been the problem with gene therapy the last ten years.

How far are we from testing that in humans?

Almost everything I've described has been done in rodents, so we're talking about years, not decades. It's shorter than the Human Genome Project [which took 13 years], not less expensive, but definitely shorter. _TechnologyReview

Scientists at the University of Toronto have recently made a breakthrough in the control of IPS cells' pluripotency:

Scientists have found a control switch that regulates stem cell “pluripotency,” the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in “adult” cells—those that had become the specialized cells that comprise organs and perform functions.

“It opens the field to the fact that alternative splicing plays a really important role in stem cell pluripotency,” said Prof. Benjamin Blencowe, principal investigator on the study and a Professor in the University of Toronto’s Departments of Molecular Genetics and Banting and Best Department of Medical Research. “We’re beginning to see an entirely new landscape of regulation, which will be crucial to our understanding of how to produce more effective pluripotent stem cells for therapeutic and research applications.”

The findings were published in the current online edition of the scientific journal Cell. _Source

These are some fascinating developments, which will eventually lead to advanced therapies for diseases which are currently untreatable, such as cancers and end stage degenerative diseases of the heart, lungs, liver, kidneys, and brain.

The ability to grow replacement organs from stem cells is already being proven in animals. The ability to regenerate a badly degenerated organ in situ, using stem cells, is also being proven. According to George Church, stem cells are also the best method for making genetic improvements to organs and organisms.

BioHeart's clinical stem cell trials in Mexico

ThermoGenesis an early commercial entrant into the human stem cell regenerative medicine industry

Regenerative Medicine Advances

The promise of regenerative medicine involves a future where replacement organs and tissues can be re-grown in a lab from a person's own cells, then transplanted into the person as brand-new, fully functioning replacement tissue. Replacement lung tissue, replacement heart tissue, replacement ligaments and tendons, replacement skin, kidneys, muscle, intestine, bladders, and on and on. But first, scientists have to find a good way to grow millions and billions of healthy stem cells from a person's own cells, and keep them alive long enough to turn them into the proper tissue, and grow them on a proper scaffold into the proper replacement organs.

Investigators from the Massachusetts Institute of Technology (MIT) recently developed a new type of support structure for stem cells, which allows them to remain alive for weeks without using any foreign genetic material.

Generally, substrates for growing stem cells contain animal cells or tissue, but these can easily contaminate the samples themselves, which means that they can lose some of their capabilities.

This is an especially serious consequence for induced pluripotent stem cells, which are biological units that can transform into any type of tissue in the human body.

Only environmental conditions dictate whether they will turn into nerve cells, or into pancreatic tissue.

Due to this amazing differentiation ability they have, these cells hold great promise for treating a number of disorders, such as for example Parkinson's, multiple sclerosis and spinal cord injuries.

But, in order to make the best of them, researchers need to be able to grow them in sufficiently large quantities, and this is proving to be extremely difficult due to the lack of proper substrates.

One of the main issues in this field of research is the fact that human stem cells are now grown with the aid of cells or proteins derived from mice embryos. If these foreign chemicals would interact with the human body, they would definitely cause an allergic reaction.

Thanks to the MIT collaborations, which includes biologists, materials engineers and chemists, scientists now have a synthetic surface that features no material from mice or other animals.

The data the team recorded of the new surfaces show that they promote and sustain “all-natural” stem cell growth and reproduction for at least three months. Longer periods are also possible, the group says.

Another impressive feat the MIT experts achieved with their new material is the fact that it allows for researchers to separate colonies of identical cells from each other. The surface allows single cells to form colonies of cells of that type with considerable ease.

Details of the new investigation appear in the August 22 issue of the esteemed scientific publication Nature Materials, e! Science News reports. _Softpedia

Another report from ScienceDaily

“For therapeutics, you need millions and millions of cells. If we can make it easier for the cells to divide and grow, that will really help to get the number of cells you need to do all of the disease studies that people are excited about,' says MIT postdoctoral associate Krishanu Saha, one of the co-first authors of the paper. 

The work was led by MIT professors Robert Langer, Rudolf Jaenisch and Daniel G. Anderson, in collaboration with Saha and postdoctoral researcher Ying Mei. _Softpedia

This report from Brian Wang on Swiss stem cell research, suggests that mature tissue-derived stem cells can be programmed across germ layer boundaries. This finding hints at the possibility of creating virtually any type of cell or tissue from any other type of tissue -- including easily sampled tissues such as skin or blood.

Cross-posted at Al Fin

Printing Out New Organs and Other Adventures in New Biology

It may not be long before severely burned persons will be able to lie back and watch while an entirely new skin is printed onto their body -- saving their lives.

The same printer technology that sits on your desk could soon be a common fixture in rebuilding human tissue, treating burns by laying down layers of a patients' own skin or even rebuilding whole organs.

A team at Wake Forest University has built a "bioprinter" that uses cells instead of ink. It even uses an ordinary, off-the-shelf printhead, connected to test tubes full of different cell types instead of wells full of colored inks.

Led by Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston–Salem, N.C., the team is working on treating burns. Such wounds can be hard to treat, because in severe cases there might not be enough healthy skin on the patient to harvest or culture for a graft.Grafting skin to cover burn wounds is also important for preventing infections, which can be a source of complications. Printing out cells grown in culture would eliminate these problems. Another application is repairing scar tissue.

The breakthrough in using bioprinting for tissue regeneration is the gel used to contain the cells: The mixture must hold the cells in place when they are laid down as well as provide a viable medium where they can be kept alive while they are held in the reservoirs. "It took us seven years," he says. "There's lots of trial and error; this isn't trivial chemistry," he adds.

For building tissue, several printing methods were tried, including three-dimensional CAD and laser printing. But once the group hit on the inkjet method, it turned out to work so well that some of the early work on building tissue was done on modified inkjet printers from a local office supply store.

Other organs have been constructed from cultured cells, but they were built on a scaffolding to give them their three-dimensional shape. Skin doesn't require a matrix because it is relatively flat to begin with.

So far, the system has been tested on mice, which are given wounds similar to burns. Those that were treated with printer-generated cells healed in three weeks, whereas those that were allowed to recover naturally required five weeks. The researchers plan to test the system on bigger animals in the future. The technology is still in the early stages, Atala says. As of yet there is no timetable for human tests or for the publication of the mouse research results.

The Wake Forest group is not just working on skin. Bone tissue and a two-chambered mouse heart have both been successfully printed. The heart was stimulated to beat when the cells were shocked with electricity, and the printed bones have been implanted in mice. _SciAm

Another approach to tissue regeneration is the use of biodegradable polymers as a scaffolding for the growth of replacement cells and tissues.

Here is an idea that is genuinely visionary -- which is exactly the sort of thinking we need to promote if we are ever to get to where we want to go. If we can take our biology to the level that allows us to grow living, breathing, thinking buildings that keep us comfortable and safe, imagine the level of accomplishment that human tissue engineering will have achieved.

A healthy, vibrant, and expansive society requires the best from all of its citizens. We cannot afford to be overly focused upon just one goal. We need to also be developing ideas and processes that may have no immediate use -- but which may indeed be earthshaking and earth saving sometime in the future.

Regenerative Medicine Roadmap

PDFRegen-RoadmapPDF
FightAging presents a look at what it describes as "The Dawn of the Age of Tissue Engineering", and presents a roadmap of regenerative medicine in PDF format. via Brian Wang

Regenerative medicine is one of several different approaches to life extension and improved human longevity.

Cell therapy involves the adding of younger or progenitor cells, the removal of senescent or destructive cells, and the genetic reprogramming of cells in situ. New and reprogrammed cells then grow within the pre-existing matrix.

Tissue engineering involves the growth of tissues or entire organs within artificial scaffolding. This growth may occur outside the body (for later transplant) or inside the body with in situ tissue engineering.

Cell therapy is the easier approach, but may take several decades of development to achieve the regenerative power that tissue engineering promises to provide within one decade.

Hormonal and growth factor regenerative medicine use chemicals to alter the cells from the outside, in a therapeutic sequence. This approach is even easier than cell therapy, but is also more limited.

There are other regenerative therapies which work via the immune system, and via epigenetic systems, and some of these will come into use within the next decade or two.

Other life extension strategies -- such as cryonics, mitochondrial rejuvenation, technological prostheses, and the total redesign of the human body -- will continue to receive varying levels of support. One should also keep an eye on SENS.

Thymosin Beta 4 Helps Regenerate Damaged Brain in Rats

The small protein thymosin beta 4 has multiple functions: it moonlights to repair injured tissues [6], has anti-inflammatory efficacy in monocyte/macrophages [7], promotes wound healing [8] and mediates angiogenesis [9]. Tβ4 has been also shown to play a relevant role during the development of different neural cell types in the rat brain [10]. In particular, Tβ4 plays a neurotrophic and antiapoptotic role during the development of the nervous system [11]. __PLoSONE

New research to be reported June 3 at the Annual Meeting of the Society for Academic Emergency Medicine in Phoenix, showed that in adult rats, thymosin beta-4 assisted in the repair of nerve fibres in the brain and in growing new blood vessels.

A synthetic version of a naturally occurring peptide promoted the creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers at Henry Ford Hospital in Detroit.

"This successful experiment holds promise for treating clot-induced strokes in humans," says study lead author Daniel C. Morris, M.D., senior staff physician in the Department of Emergency Medicine at Henry Ford Hospital. "Neurorestorative therapy is the next frontier in the treatment of stroke." _SD

This is a potentially important finding for regenerative medicine, given how common cerebral vascular accident is in humans, and how dismal the prognosis typically is afterward.

Thymosin beta-4 is an immune modulating protein, which demonstrates once again how important the brain and the immune system are to one another. Given that Thymosin beta-4 is not a growth factor, as such, it will be important to generate a picture of the entire mechanism involved, for a complete understanding of potential therapies for brain damage, using this protein.

Human Cell Aging Reversed by Biotime

Biotime researchers report the successful resetting of the "age clock" of mature human cells back to the embryonic age. This was apparently accomplished using telomeric technology similar to what Geron has been working on.

In the article, BioTime and its collaborators demonstrate the successful reversal of the developmental aging of normal human cells. Using precise genetic modifications, normal human cells were induced to reverse both the "clock" of differentiation (the process by which an embryonic stem cell becomes the many specialized differentiated cell types of the body), and the "clock" of cellular aging (telomere length). As a result, aged differentiated cells became young stem cells capable of regeneration.
_NextBigFuture

More links, videos, and information from Brian Wang and at the BioTime website.

Regenerative Medicine Gets a Boost

Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants. _TechnologyReview

Salk Institute researchers in La Jolla have demonstrated a technique that opens the door to cures for several genetic blood diseases. It involves taking a patient's skin cells, treating them genetically to correct the inherited disorder, next turning the skin cells into induced pluripotent stem cells (iPS), then differentiating those iPS into progenitor cells. These progenitor cells can be implanted into the patient to provide a supply of normal blood cells.

"This is an exciting bit of science," says Chris Mason, a professor of regenerative medicine at University College London, who was not directly involved in the research. "It's likely to be the first of a slew of similar papers that may offer hope for conditions where today there is no real therapy, let alone a cure."

So far, Belmonte's approach is applicable only to diseases in which the genetic defect that underlies the disease has been identified. "But there are quite a few of these--and the number will increase," says Mason. Blood disorders are likely to be the first targets for therapy because corrected cells can easily be transferred back to the patient via bone-marrow transplants.

Belmonte adds that in the future, the correction of more-complex genetic disorders might become possible, thereby significantly increasing the number of diseases that might be treated with altered iPS cells. _TechnologyReview

If the bone marrow can be "re-stocked" with viable normal blood progenitor cells, the inherited blood disorder may indeed be cured. The concept can be extended to other inherited and acquired genetic diseases with extensive work.

Such approaches to cell and tissue replacement open the door to significant extension of maximum life span.

Taken from an earlier post at Al Fin

Australian and American Researchers Team to Advance Regenerative Medicine Strategies

When humans can grow new organs to replace tired or damaged organs, we will transcend one of the reasons for too-early death: organ failure. Every advance in the field of regenerative medicine is a positive step toward that goal.

John Foster's Bio/Polymer Research Group at the University of NSW worked out in 2004 the correct wavelength of infra-red laser to seal sheets of the university's patented discovery, SurgiLux, over wounds.

Now Foster is teaming up with Stephen Badylak, pioneer of the extra-cellular matrix, at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. Badylak creates ECM from ground-up pig organs. It acts as a scaffolding material for wounds and can be absorbed by the body. Cells spontaneously regrow on it and adult stem cells are attracted from other parts of the body, developing into tissue similar to the original.

These scaffolds have helped more than one million people regrow cartilage, rebuild urethras and repair hernias.

Foster and Badylak hold high hopes for the marriage of their technologies now that Foster has been awarded aFulbright senior scholarship that will fund him for up to four months' work with Badylak's group from June next year. The aim is to develop the technology to support the surgical repair ofnerves. _Australian

Growing new cells and tissues in the proper mix of cell types with neurovascular and lymphatic support, will require precise methods and timing. Learning how to best attach the new cells, tissues, and organs to the rest of the body is a vital part of the regenerative picture.

More Engineered Stem Cell News

Toronto's Samuel Lunenfeld Research Institute at Mt. Sinai Hospital is the site of groundbreaking research on engineered stem cells.

"We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable," said Dr. Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Investigator at the McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration. "This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues such as a patient's own skin cells."

Dr. Nagy discovered a new method to create pluripotent stem cells (cells that can develop into most other cell types) without disrupting healthy genes. Dr. Nagy's method uses a novel wrapping procedure to deliver specific genes to reprogram cells into stem cells. Previous approaches required the use of viruses to deliver the required genes, a method that carries the risk of damaging the DNA. Dr. Nagy's method does not require viruses, and so overcomes a major hurdle for the future of safe, personalized stem cell therapies in humans.

"This research is a huge step forward on the path to new stem cell-based therapies and indicates that researchers at the Lunenfeld are at the leading edge of regenerative medicine," said Dr. Jim Woodgett, Director of Research for the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. Regenerative medicine refers to enabling the human body to repair, replace, restore and regenerate its own damaged or diseased cells, tissues and organs. _PO

The new method avoids the risks of tumourogenesis that come with using viruses for reprogramming cells into stem cells. Various new and potent techniques of producing virtually any stem cell type from adult cells bring modern biomedicine ever closer to the ability to replace and / or rejuvenate virtually any tissues in the body -- using the person's own cells!

There is still much to be learned about the genetic switching mechanisms involved. Until we are certain that the re-programming techniques can truly provide safe, long-lived replacement cells for the various tissues of the body, we will need to continue experimenting with embryonic stem cell lines as well as with the re-programmed stem cells.

Genetically Modified Regenerative Skin Graft Material Designed to Resist Infection

Stratatech’s StrataGraft® tissue is a second-generation human skin substitute that exhibits normal human skin structure and function. It is manufactured using the company’s proprietary NIKS® human keratinocytes, which were discovered at the University of Wisconsin. Keratinocytes are the cells that make up approximately 90 percent of the epidermis, the outer layer of human skin. NIKS® cells are a consistent source of pathogen-free, non-tumor-producing, long-lived adult progenitor cells. These cells faithfully reproduce normal human skin tissue architecture and barrier function when cultured appropriately. _StratatechCorp.

Regenerative medicine company Stratatech Corporation has developed a genetically tweaked living skin substitute for use in skin grafting. The genetic modifications of the living skin replacement makes it far more resistant to infection than currently available skin graft materials -- including autologous skin grafts.

The anti-infective capacity of Stratatech’s genetically-engineered tissue, which is being developed and commercialized by the company as ExpressGraft™ Enhance skin substitute through a worldwide exclusive license from the Wisconsin Alumni Research Foundation, or WARF, is produced by genetically engineering the elevated expression of a naturally-occurring antimicrobial host defense peptide called hCAP-18/LL-37. hCAP-18/LL-37 was selected because of its broad antimicrobial activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus (MRSA), vancomycin-resistant E. faecalis (VRE) and other antibiotic-resistant hospital-acquired infections, as well as some fungi and viruses. The enhanced tissue possesses a full-thickness structure and barrier function similar to that of native human skin. The cell type used to generate the ExpressGraft™ tissue has been demonstrated to be non-tumor-producing and free from detectable pathogens, characteristics critical for cell-based, regenerative medicine therapies for patient use.

“Bacterial infection is a substantial cause of skin graft rejection and additional health care costs,” said Lynn Allen-Hoffmann, Ph.D., Stratatech’s founder, chief scientific officer and chief executive. “The potent anti-infective capability Stratatech has engineered in our living human skin substitute can be an important tool in improving skin-injury patient outcomes, and reducing the incidence and expense of hospital-acquired infections. We look forward to beginning the clinical evaluation of our antimicrobial skin substitute in the near term.

...Stratatech’s genetically-engineered skin substitute was generated using a non-viral vector, or carrier. The company believes it is the first time a virus-free approach has been used to genetically modify a living, cell-based tissue substitute. The data published in Molecular Therapy demonstrate that the modified tissue contained 139-fold more anti-infective proteins called host defense peptides than unmodified tissue in vitro. _BusinessWire

This is only the beginning of genetically improved, artificially grown bio-replacement materials. This skin replacement product from Stratatech should do well in the marketplace if it lives up to its promotion. But expect competing products that improve on the ExpressGraft's performance to emerge before long. This graft material does not perfectly reproduce the full, intricate layered structure of natural skin. But it is a good start.

Other more intricately structured grown replacement parts should follow on rather quickly. We are entering the age of regenerative medicine, when body parts and tissues will be grown in labs, rather than being donated by accident and crime victims. If these replacements can be designed to be tougher than the original parts being replaced, all the better.

Constructing New Infrastructure for Regeneration

Tissue scaffolds are the next big thing for implants of the future. Like the scaffolding we see on construction sites, the nano scaffolds are being created by Ko to reconstruct damaged tissue within the human body. Burn victims would benefit from scaffolds used to regenerate new skin. Those with failing heart valves or damaged nerves could count on scaffolds to regenerate these parts from within the patient’s own body. As healing progresses, the scaffold, being constructed from a biodegradable material, is absorbed and metabolized by the body while slowly releasing drugs to aid in the healing process. _CyborgAge

Almost every part of the body presents opportunities for scaffold bio-engineers to experiment. From the heart to the spine to the skin, all parts of the body eventually wear out and need to be replaced or regenerated. Scientists at UC Berkeley are taking an entirely new approach to bio-scaffold development. They are using viruses (bacteriophages) to build a proteinaceous infrastructure that promotes regeneration of nerve tissue.

Some biological engineers are using scaffolds made of polymers to try to mimic the supportive matrix of real tissue. Seung-Wuk Lee, a bioengineer at the University of California, Berkeley, has turned to viruses instead. "Viruses are smart materials," he says. "Once you construct the genome, you can make billions of phages, and they're self-replicating materials." The phage that Lee is working with, called M13, is long and thin like the protein fibers that make up the cellular matrices inside the body.

First, Lee and his colleague Anna Merzlyak genetically engineered M13 to display nerve-friendly proteins on their outer coats. These proteins are known to help nerve cells proliferate, adhere, and extend into long fiberlike shapes. Next, the researchers grew large numbers of the viruses in bacterial-cell hosts and dropped them into a solution containing neural-progenitor cells. These cells are more fully developed than stem cells but are still young and need coaxing to form new tissues. In the solution, the viruses align themselves like a liquid crystal, says Lee. He and Merzlyak used pipettes to inject the solution into agar, a Jell-O-like cell-culture medium, creating long, nerve-like fibers of the virus interspersed with cells. The progenitor cells then multiplied and grew the long branches characteristic of neurons. Lee says that the phage are well suited to making long, fiberlike structures such as nerve tissue but can also be made into more complex structures by varying their concentration or manipulating their position with a magnetic field. _TechnologyReview

Lee is planning to move to research inside live animals next. He is interested to discover how the immune systems of animals will react to viral construction workers hammering, drilling, and welding new infrastructure deep inside the organism.

For regenerative medicine to take that next big step forward, it will need the ability to grow specific infrastructure for every tissue and organ type that will be replaced or regenerated. Then, scientists will need to integrate growth factors and stem cells into the new matrix, and provide optimal nutrient solution. The prognosis for significant progress in this area is extremely favourable.

Nerve Regeneration Gene Pathway Discovered

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Research at the University of Utah has pinpointed specific genes in worms that appear to trigger nerve re-generation, and make old worms behave like younger friskier worms when the genes are over-expressed.

"One of the coolest things is we can improve regeneration," Nix says. "We originally looked at loss of this gene, dlk-1. The loss blocks regeneration. We can cut the nerve in these mutants and they don't regenerate. So we see worms with nerve stumps that don't do anything. But when we overproduce dlk-1 make an excess amount of it then we see an improvement in regeneration."

Jorgensen an investigator with the Howard Hughes Medical Institute says that "normally, young worms regenerate really well; old worms don't regenerate at all. What we can do by overexpressing dlk-1 is make old worms regenerate like young worms."

The chain of events the researchers identified as playing an essential role in nerve regeneration is known as a "MAP kinase pathway." Various MAP kinases play roles in cell division, response to stress, and cell specialization, Jorgensen says.

The pathway discovered in the new study "is unique in that it is not used by the nervous system during normal embryo development, yet it is absolutely required for regeneration," Bastiani says. "Most of us believed that virtually everything we found in regeneration also would be involved in development. So it is surprising."

He says while the dlk-1 gene is the most obvious target for new drugs to stimulate nerve regeneration, other genes in the pathway also could be potential targets. _GEN

Humans possess the same sets of genes that were studied in worms. It remains to be proven whether the genes have the same effect in humans for nerve regeneration, as in worms.

We are finding that older cells become leaky and let more damaging substances into their nuclear compartments, where DNA becomes damaged. Better means of preventing nerve damage and reversing that damage are beginning to come within the grasp of science.

Replacement Body Parts

Since 1967, when Christiaan Barnard successfully performed the first successful human to human heart transplant, it has been painfully obvious that there are not enough human hearts available to meet the demand. Surgeons have tried various approaches to replacing damaged and worn out hearts--including baboon hearts, refrigerator sized machine replacement hearts, and most reacently, the AbioCor totally implantable artificial heart system. While the AbioCor's batteries can be rechared through the skin, they will eventually have to be replaced. Machine hearts are subject to failure of various types, and experience with them is still only short term.

Eventually, hearts will be "printed", along with other replacement organs. Other organs, such as the urinary bladder, have already been synthetically produced and implanted. But the heart's fibrous skeleton is too complex for scientists to mimic in the lab--to this point.

So lab scientists are learning how to scavenge heart skeletons wherever they can. University of Minnesota scientists have taken dead animal hearts and removed the dead cells--leaving the fibrous infrastructure. By injecting immature heart cells into the scaffolding--in a stepwise manner--they were able to revitalize the heart to the point of beating.

The team took a whole heart and removed cells from it. Then, with the resulting architecture, chambers, valves and the blood vessel structure intact, repopulated the structure with new cells.

"We just took nature's own building blocks to build a new organ," says Dr Harald Ott, a co-investigator who now works at Massachusetts General Hospital. "When we saw the first contractions we were speechless."

The work has huge implications: "The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells," said Prof Doris Taylor, director of the Centre for Cardiovascular Repair, Minnesota, principal investigator.

The method could be used to grow liver, kidney, lung and pancreas, indeed virtually any organ with a blood supply.

Telegraph

In the meantime, researchers continue to work on alternatives--including artificial hearts that spin like a turbine, producing a constant blood pressure rather than a pulse. Such turbine hearts are said to be efficient in small sizes, making it easier to fit size constraints. Such hearts would still have the problem of requiring a power supply.

Rather than replacing the heart, methods of regenerating the existing heart are being developed. Techniques of injecting stem cells into the patient's heart have already produced positive results in some cases. Likewise, procedures that attach "sheets of muscle blasts" to the patient's heart have been successful in Japan. Clearly, it would be preferable if the patient's own heart can serve as a scaffold for cell replacement.

In several pathological processes, however, the underlying structure of the patient's heart has been rendered dysfunctional. Without extensive remodeling surgery, the heart's infrastructure has to be replaced.

In approaching heart replacement, patients, physicians, and families have to weigh the benefits and risks. With the rapid growth in viable choices for replacement, this process will necessarily become more detailed and informed.

Bioprinting organs, and other ways of regenerating or synthetically reproducing human organs, will be very expensive for a long time. That expense will push experimentation in different directions.

Originally published in Al Fin

Regenerative Medicine--A New Approach to Embryonic Stem Cell Replacement Tissue

Imagine if you will, being able to grow embryonic stem cells to regenerate your failing cells, tissues, and organs--just from your own sperm or eggs. No need to create a fertilised zygote or mated embryo, so there should be no ethical objections from anti-abortion politicians and their constituents.

In the February 15th issue of G&D, Dr. K. John McLaughlin and colleagues report on their success in using uniparental embryonic stem cells to replace blood stem cells in mice. Uniparental embryonic stem cells are an appealing alternative source of patient-derived embryonic stem cells, as they have several advantages over embryonic stem cell lines generated by somatic cell nuclear transfer (also known as therapeutic cloning).

....This study shows for the first time that parthenogenetic blood cells can replace those of an immunocompromised adult mouse. McLaughlin and colleagues also show that this is also possible using embryonic stem cells where both genomes are solely derived from sperm of one male (androgenetic), adding fertile males to the potential patient pool.

....The researchers took a two-step approach: First they injected uniparental ES cells into wild-type blastocyts to generate chimeric animals; then they harvested these chimeric fetal livers for transplant into lethally irradiated hosts. The scientists found that uniparental ES cells, regardless of parent-of-origin, were able to functionally reconstitute the entire hematopoietic system of adult mice. Furthermore, the scientists were also able to grow progenitor blood cells in culture from uniparental ES cells, and upon transplant into irradiated adult mice, show that these cells contribute, long-term, to the function of their hematopoietic system.

Source.

In other words, using either only eggs for a female or only sperm from a male, researchers were able to grow embryonic stem cells as replacement blood cell progenitors. These replacement cells functioned and kept the mice alive.

There are still issues of "imprinting" to be worked out when attempting to regenerate different body tissues from asexually produced ESC's. But at least the cells from this approach would be immunologically compatible with the donor. Immunological compatibility is something that sexually produced ESC's cannot guarantee, for purposes of organ regeneration.

Either way, it will be several years before humans can take advantage of this new opening in regenerative medicine.Some feminists had hoped that only females would be able to produce viable ESCs by the asexual method. They had hoped to use that leverage to force males in the US Congress to vote for unlimited funding for nuclear transfer and cloning technologies to produce new stem cell lines.

My question is--why not do both? I am constantly disgusted by the leftists who try to minimize the importance of non-embryonal approaches to creating stem cells, just as I am disgusted by the religious rightists who try to make every technology that deals with haploid cells into an abortion issue.

Unfortunately both groups of closed minded individuals have their own areas of power--where they work to limit our choices. Too bad.