The history of organ transplant and stem cell research is rich in optimism, yielding promising results from in vitro and animal model studies that would greatly impact the landscape of medicine. Translating these findings into bedside medicine is the next hurdle to overcome. Understandably, this was an issue that frustrated the early pioneers of the field. Past Nobel Laureates in Physiology or Medicine, Alexis Carrel and Sir Peter Medawar, hypothesized about a “biological force” that prevented successful transplantation and how the force “forever will inhibit transplantation from one individual to another” [1]. This “force” today is known as the immune system and its recognition of the human leukocyte antigen (HLA) that is unique to each individual. Thanks to the Nobel Prize work of Dr. Donall Thomas on graft-versus-host disease, this is an issue that can be mitigated through irradiation of bone marrow and immunosuppression [1].
The challenge going forward in stem cell research is addressing critical issues that plague medical practitioners daily. First consider a patient post-myocardial infarction with irreversibly damaged cardiomyocytes who is now susceptible to arrhythmias. Stem cell research is now at a point where mouse models have shown the ability to regenerate heart tissue through systemic infusion of cardiac adipocytes derived stem cells (CA-AdSCs) into an ischemic myocardium, improving cardiac function through differentiation to endothelial cells, vascular smooth cells, and cardiomyocytes [2]. These results could translate into CA-AdSCs being used as an effective regenerative medicine candidate for myocardial ischemia therapy. The second example would be an individual with an autoimmune disease (Systemic Lupus Erythematosus, SLE, or Type 1 Diabetes) whose disease may not be responsive to immunosuppression. Rigorously screened (HLA matched) and intravenously infused umbilical cord stem cells from Wharton’s jelly has been shown to improve renal function and decrease a non-placebo-controlled study for 40 individuals with SLE [3].
A relatively new topic in stem cell research is the functional restoration of endogenous pluripotency factors by epigenetically transforming terminally differentiated cells into embryonic stem cell-like cells, also known as induced pluripotent stem cells (iPSCs) [4]. This is an ingenious approach to bypass the ethically and politically controversial topic of harvesting embryonic stem cells. A recent application of this technology involves deriving iPSCs from terminally differentiated skin cells to create a kidney organoid containing functional nephrons [5]. These ex vivo kidney organoids are similar to fetal first-trimester kidneys in their structure and physiology. Such kidney organoids can serve as models for nephrotoxicity screening of drugs, disease modeling, and organ transplantation, with the latter being more hypothetical than applicable due to organ maturity, size, and capacity.
These are just a few highlights of what is new in stem cell research and what the future looks like in terms of regenerative medicine and stem cell therapy. In our lifetime, we will see these in vitro and animal model research being translated into clinical settings. After all, it takes an average of 17 years for research evidence to reach clinical practice [6].
Ogaga Ojameruaye is a medical student at The University of Arizona College of Medicine – Phoenix. He completed his BS in physiology at The University of Arizona and completed his MS in psychology at Grand Canyon University. Ogaga is passionate about translational medicine, bench-to-bedside research, and the discovery of new diagnostic tools as they contribute to the model of precision medicine.