Solving the Challenges of Stem Cell Tissues
Everyone has heard buzz around stem cell research, artificial organs and tissue engineering, and now becoming educated on the politics and science of these topics is increasingly important. These innovative fields make up the future of regenerative medicine, which is the process of creating living tissues that function just like naturally grown tissues with the goal of replacing malfunctioned or damaged tissues or organs.
Pluripotent stem cells are the basis of differentiating unspecified cells into various types of cells such as liver, epithelial, and intestinal. These differentiated cells are then engineered into tissues that mature to carry out those assigned tissue’s functions. Although there are many challenges involved in the puzzle of human stem cell science, this article focuses on three common encounters faced upon evaluating cell-host interactions. Upon implantation of the engineered tissue into the host, the stem cell tissue can suffer from poor or absent tissue function, host immune rejection, and tumor formation from undifferentiated cells. Scientists all over the world have been conducting research to solve to these challenges with different stem cell lines, various tissue combinations, and cocktails of growth factors. The future of regenerative medicine lies in our ability to solve these natural challenges in stem cell tissue implantation.
Among the first major challenges in stem cell tissue engineering history was getting artificial tissues to function adequately upon implantation. Since the entire premise of regenerative medicine is to correct a tissue’s failed or sub-par function, it’s vital that the engineered tissue will be able to perform just as natural tissue upon implantation into the host. Researchers quickly learned that a separate, acellular, stable 3-D matrix was needed to grow the stem cells in a petri dish for a specific amount of time with an exact amount of growth factors and nutrients (varies based on type of stem cells and tissue desired). After much trial, error, protocol revision, and collaboration, various tissues are undergoing animal studies to prove their functionality in vivo. Scientists at Cincinnati Children’s Hospital Medical Center developed a functioning intestinal tissue that successfully absorbed nutrients and collaborated with the host’s tissue on peristaltic motions in their preliminary animal trials. Upon completion of many repeatable, successful preliminary animal implantation trials, scientists will need to determine if this engineered tissue is successful in functioning alongside diseased tissue in the host and continue to carry-out its function. Every tissue needs to be tested in vivo under unhealthy conditions to prove that it will deliver the same results to treat or replace the diseased tissue.
The most common challenge in stem cell tissue engineering is host immune rejection of the new tissue upon implantation. An engineered tissue can be perfectly grown and exceedingly functional; however if it is not a match for the host’s tissue or if anything in the implanted tissue creates a negative response in the host, a cascade of immune responses will be initiated for the host to reject the implanted tissue. This natural response can be triggered by any factor that the immune system considers potentially harmful to the host, such as non-host cells, foreign matter, increased growth factors, or mis-folded proteins. Scientists at Gregorio Maranon University Hospital have developed a method to engineer tissues for transplant with very low likeliness of host rejection by developing the new tissue with the host’s own stem cells. Their method involves extracting adult adipose-derived stem cells (ASC) from the host and growing them in an acellular scaffold appropriate for the tissue or organ being developed. They grow this culture in vitro in a bioreactor prior to host implantation. So long as the implanted ASCs are from the host and the bioreactor process has been accurately carried-out, the host should not have an immune rejection response to the new tissue. This research is the frontier methodology used today in tissue engineering and research centers internationally are taking advantage of the power of ASCs.
The most potentially lethal challenge in stem cell tissue engineering is the possibility of tumor formation from undifferentiated cells in the implanted artificial tissue. Engineering tissue from stem cells is ideal because those cells can differentiate into new functioning tissues of various types, however among the hundreds of millions of cells making up the life-saving tissue, there may remain several undifferentiated cells (these are cells that are remain multi-potent). Upon implantation and assimilation of the new tissue with the host tissue, it is possible for these undifferentiated cells to form teratomas, which can potentially grow into a lethal tumor. The Stanford Institute for Stem Cell Biology and Regenerative Medicine has discovered a way to remove the undifferentiated cells from the engineered tissue prior to human implantation. Their research utilises a monoclonal antibody-based protocol that recognises and binds to glycan on undifferentiated cells, which causes these cells to separate from the tissue and enable scientists to remove only those marked cells from the new tissue.
Although there are many political and scientific hurdles that need to be overcome, the future of regenerative medicine is strongly racing forward. Research and clinical trials are underway internationally to overcome the three major stem cell implantation challenges mentioned in this article, which is pushing us closer to developing therapies that can alleviate chronic and lethal illnesses. Staying educated on the future of regenerative medicine is vital to the industry’s growth because these scientists are engineering the future of healthcare.
Cincinnati Children’s Hospital Medical Center
Stanford School of Medicine