Wednesday, June 27, 2012

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.
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.
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.
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.

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