Liver Transplantation from Stem Cells

“Liver Transplantation: Is there a better method in our future?” This topic was prescient because I frequently hear about how difficult organ transplantation is, and the cocktail of drugs currently used to suppress the immune system from rejecting the organ is quite harsh. It’s a pressing need affecting millions of people worldwide, and an excellent topic.

The slide of indications for a liver transport was good, it’s almost impossible to cover every reason a liver transplant is performed. This issue will be discussed later in this review, where I’ll attempt to find literature with novel pathologies for liver transplantation. Moving on towards the necropsy portion where the liver is removed, I did not realize the process involved an individual who was fully deceased. I had assumed the liver transplant was performed on brain dead patients, but that prospect is intriguing. It seems the liver is a resilient organ, then. The following slide discusses the constant shortage of organs, most likely predicated on the advancement of diagnostics for liver failure etc. The cadaver issue was addressed in detail in the next slide. Partial liver transplants is a strongly coordinate process, and it is encouraging to know stem cells are on the brink. The next three slides discuss the development of stem cells, and intricate discussions of rat models. The hallmark study used in the presentation was developed in 1991. It took approximately 11 days for mRNA to develop. This frame seems reasonable, but the transition to human development has not moved as quickly. The scaffolding aspect of Hoganson’s 2008 growth is the most interesting aspect. Structurally uncontrolled growth would not be an ideal clinical situation. The uncontrolled growth was addressed in the consequent slide, the risk of metastatic cells being placed in vivo is less than not having a liver itself. I’d have to concur with the seeming slowness of progression in the past twenty years. That’s an unfair assumption, clearly; as the presentation was simplified for digestibility. It would be interesting to discover the efficacy of embryonic stem cells vs somatic cells, but this is not urgent. If e stem cells are efficacious, it might be an insistent discovery. The listing of contraindications for liver transplantation is even higher than discussed. The ethical implications of that is likely overwhelming. Rarer autoimmune diseases, Budd-Chiari syndrome are also adequate indications for hepatic transplantation. Growing a liver from stem cells presents considerable scaling challenges. Other groups have invested time in repairing livers without needing full transplantation, and the literature is limited for full tissue re-engineering on that scale, even in closed-source journals. Tissue engineers have closely examined growing ex vivo hepatocytes derived from stem cells, however. Liver growth in culture is not currently ready for clinical trials (Soto-Gutierrez, et al. 2011). One of the difficulties represented with administering hepatocytes to a damage liver is that they are slow-growing and not precisely identical. This can be partially remedied via a process called scaffolding. It allows the hepatocytes to grow in a manner where they can be inserted into a decellularized liver. Enzymes and detergents destroy the faulty cells and the process prepares the medium for invigoration. The hepatocytes are then injected into the necrotic liver either immediately or infused over time. This is less energy intensive than whole organ transplantation. The liver retains most of its capabilities. This study was just completed in rats, so human trials are even further away than the methods described by Douchette. Soto-Gutierrez, A., Zhang, L., Medberry, C., Fukumitsu, K., Faulk, D., Jiang, H., Reing, J., Gramignoli, R., Komori, J., Ross, M., Nagaya, M., Lagasse, E., Stolz, D., Strom, S.C., Fox, I.J., Badylak, S.F. 2011. A whole-organ regenerative medicine approach for liver replacement. Tissue Engineering Part C Methods. Jun;17(6):677-86.

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