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.

A Brain Zapping Method of Removing Unwanted Nerve Connections

Scientists at the University of Western Australia have devised an intriguing method of removing unwanted neural connections in mice. Whether or not this procedure is directly applicable to humans, it opens a world of possibilities for improving the mental lives of a wide range of persons at every stage of life, from early onset schizophrenia through the brain maladaptations of senescence.

One of the pillars of Aubrey de Grey's Sens approach to anti-ageing is the removal of malfunctioning cells in the body. There is an analogous need in the brains of many individuals to remove malfunctioning or excess nerves and nerve connections, to optimise or improve brain functioning. Here is more on the experiments in mouse brains:

Jennifer Rodger from the University of Western Australia in Crawley and colleagues have found that stimulating the brain at intensities lower than would make a neuron fire can remove unwanted neural connections in mice.

As children, our brains produce too many connections between cells. As we develop, some connections are pruned away while others are strengthened. Inept pruning has been implicated in schizophrenia.

Rodger's team used genetically modified mice with abnormal connections in an area of the brain called the superior colliculus (SC), which is involved in motion detection. In these mice, 90 per cent of the axons in the SC had extended into the wrong areas. These bad connections make it difficult for the rodents to follow moving objects in their line of sight.

Rodger used low-intensity, pulsed magnetic field stimulation (PMF) on the rodents' SC for 10 minutes a day over two weeks. It is thought that PMF is too weak to make healthy neurons fire. But after treatment, tissue analysis showed that only 45 per cent of the abnormal axons were still there. "The axons that weren't in the right place were wiped out," says Rodger. After treatment the mice were also better at tracking objects.

"PMF is awakening unwanted connections, so the brain can detect and remove them," says Rodger.

Unwanted neurons generally express high levels of a specific NMDA glutamate receptor. According to Rodger, this makes them sensitive to changes in electrical activity and so even low-intensity pulses can activate these neurons.

NMDA receptors send out signals that trigger the recruitment of two chemicals called nitric oxide and brain-derived neurotrophic factor (BDNF), which help remove abnormal circuitry in healthy brains. Indeed, modified mice given PMF expressed higher levels of both chemicals, while only minor changes were found in healthy mice or those given a sham procedure (The FASEB Journal, DOI: 10.1096/fj.11-194878).

"I think it is a very promising avenue for treatment of nervous system disorders that involve abnormally abundant and inaccurate connections," says Rodger. _NewScientist

The brain is in a constant state of plasticity and re-shaping throughout life. But the brain often ends up in malfunctioning or maladaptive states which can be difficult to re-shape, without outside assistance. Part of the problem may lie in the genomics or gene expression of receptors or ion channels -- leading to consequent problems at higher levels of neuron function and the function of neuronal assemblies. Optimally, the underlying genetic or epigenetic cause would be corrected. But that isn't possible in most cases -- not yet.

In the meantime, workaround solutions such as the one discovered by the Australian researchers, may well allow for cruder fixes that can still add significantly to the quality of a person's mental existence.

The challenge in this case is to not only remove unwanted nerves or neural connections. One must also be able to stimulate growth of new neural connections in more optimal configurations.

Precious Metals vs Cancer: Platinum, Gold, and Silver

Platinum was the first precious metal to achieve recognition as an effective cancer therapy:

The first platinum based chemotherapy drug discovered by researchers was cisplatin, which forty years later continues to have applications in certain types of cancer. In that time, scientists have searched for ways to improve the anti-tumor efficacy of platinum based drugs, reducing the toxicity profile, and strengthening them against resistance by expanding the class to include several new analogues of cisplatin and putting them through clinical trials to broaden the different types of cancers against which they can be safely used. _Source

Gold has more recently been recognised to have utility in fighting cancer. Gold is being used to help locate tumours and cancer cells for radiation treatment, and is also being used in drug complexes, for its cytotoxic properties.

In the last few decades the properties of gold compounds have been of interest as potential cancer treatments. Researchers at the National University of Singapore have patented novel gold complexes for use in pharmaceuticals for the treatment of cancer.

Associate Professor Leung Pak Hing and his team have discovered that phosphine supported gold complexes have excellent anti-tumour activity and clinical trials are likely to begin in the near future.

In some cases, new technologies rely on the ability of tiny gold nanoparticles to specifically collect in a cancerous tumour by passing through the inherently leaky blood vessels attached to a tumour. So, when injected into a patient, there is a means by which a potent anti-cancer compound attached to a gold nanoparticle, can be directly and accurately delivered to a tumour whilst avoiding healthy body tissue. Such an effective drug delivery mechanism with reduced toxicity is considered to be a major step-forward. Why use gold as the delivery mechanism? Well gold has a major advantage in being a very biocompatible metal. For example, colloidal gold has been safely used for over 70 years to treat rheumatoid arthritis, and many hundreds of years as a dental restoration. _AzoNano

Even more recently, silver is being seen as a potentially effective anti-cancer material.

Previous studies have hinted that silver compounds could also kill cancer cells. So Charlotte Willans from the University of Leeds, UK, and colleagues subjected silver to the same treatment as platinum to see if they could make an effective cancer drug.

The team attached different types of carbene ligands to the silver atoms before incubating varying concentrations of the compound with breast and colon cancer cells for six days.

The silver complexes proved to be as effective as cisplatin in attacking both types of cancer cells. Complexes containing a ligand which had two bonds were more effective than those with a single bond, probably because they are more stable - meaning the compound breaks down more slowly and is active for longer (Dalton Transactions, DOI: 10.1039/C2DT12399A).

Crucially, silver is less toxic to normal cells than platinum. Willans says it is an important step in the quest for effective, non-toxic cancer treatments. _NewScientist

More on the use of silver to treat cancer

The use of precious metals to treat cancer is one more reason to value them for their intrinsic worth. In developed societies, cancer is responsible for more lost years of life than virtually any other disease.