(l to r) Akiva Marcus, PhD, MD/PhD program, UMDNJ-Robert Wood Johnson Medical
School (RWJMS); Dale Woodbury, PhD, assistant professor, Department of Neuroscience
and Cell Biology, RWJMS; Kathleen Reynolds, BS, research teaching specialist;
and Thomas Coyne, Phd, MD/PhD program, RWJMS
S
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tem cell therapy represents a novel approach to the treatment of disease that may revolutionize medicine in this century. Debilitating diseases such as osteoarthritis, diabetes and Parkinson’s disease are probable candidates for future stem cell therapies. Treatment of such a diverse group of disorders, each affecting different organs, may be beyond the scope of a single stem cell population. Widespread clinical success may require an armament of disparate stem cells, isolated from multiple sources and stages of development. As science has shed light on both the potential and the limitations of embryonic and adult stem cells, interest in stem cells from the afterbirth, or extra-embryonic tissues, has intensified. Much research is needed to determine the relative potency of extra-embryonic stem cells, but they are likely to be welcome additions to future therapeutic arsenals.
Stem cells have two defining properties: multipotency and self renewal. All stem cells have the ability to produce more than one type of differentiated cell, and are by definition multipotent. Generation of these mature cells must be accomplished without depleting the original stem cell population, a feat accomplished through stem cell self-renewal. The most striking demonstration of these traits is seen in hematopoietic stem cells. These bone marrow stem cells continually produce the multitude of diverse cell types found in the blood, and can perform this task for more than a century in long-lived people.
Stem cells are quite rare, but widely dispersed. Research suggests that stem cell populations are present in most, if not all, adult tissues. In humans, stem cells have been isolated from all stages of ontogeny, from pre-implantation embryos to post-mortem adult tissues. While all are multipotent, stem cells isolated from early in development may be the most pliable, able to differentiate into a wider array of mature cell types with minimal coaxing.
The Promise of Stem Cells
The last century has witnessed striking advances in the treatment of disease. Numerous pharmacological agents have been produced that ease suffering and prolong life, but these interventions do have limitations. Drugs have to be administered frequently, and achieving proper dosing can be challenging. Targeting specific organs is difficult, and disconcerting side-effects can result. For some disorders, viable pharmacologic approaches simply don’t exist. These constraints have generated interest in stem cell-based therapies that may treat diseases in novel ways and bypass some or all of these limitations. However, before stem cells can be used in the clinic, fundamental questions concerning potency, efficacy and safety must be addressed through basic research.
The Ira B. Black Center for Stem Cell Research (IBBCSCR)
The Stem Cell Research Center at UMDNJ-Robert Wood Johnson Medical School was established in June 2002. Its mission, under the direction of Dr. Ira Black, was to provide a research environment for the investigation of stem cell plasticity. To date, the Center has supported the studies of medical fellows, postdoctoral fellows, medical students and MD/PhD students. Undergraduate students from neighboring Rutgers University have also studied here. Following Dr. Black’s death in January 2006, the Center was renamed in recognition of his pioneering efforts to advance stem cell research in the State of New Jersey. The Center continues to provide a fertile training environment for future scientists.
Figure 1. Cells migrating from an explant of human amnion form the basis of a population that can be greatly expanded in culture. Stem cells from amnion and other extra-embryonic tissues may play a role in future cell-based therapies. |
Research at the IBBCSCR examines the potency, or plasticity, of diverse stem cell populations. Our initial studies examined the plasticity of marrow stromal cells (MSCs) in vitro and in vivo. MSCs can be isolated from adult animals and traditionally have been considered stem cells for mesenchymal tissues, including bone, fat and cartilage. Recent studies have demonstrated that MSCs can be persuaded to generate completely unrelated cell types such as brain cells, liver cells and lung cells. These findings, combined with the relative ease of MSC isolation from the bone marrow, suggest that these stem cells may be ideal for the treatment of a wide range of diseases, including disorders of the nervous system. In practice, this may not be the case. When we transplanted MSCs to the adult rat brain, they were recognized as intruders and viciously attacked by the resident brain cells. All the donor cells were dead or dying within one week of transplantation. This unanticipated finding indicated that inherent characteristics of individual stem cell populations may affect their suitability for the treatment of a specific disorder. These results further suggested that the wide-ranging clinical success of stem cell-based therapies will likely require an arsenal comprised of diverse stem cell populations.
Against this backdrop, we have embarked on a new endeavor to isolate additional stem cell populations from novel sources. Our efforts have centered on the afterbirth, an assemblage of extra-embryonic tissues that nurture and protect the growing fetus during development. All constituents of the afterbirth appear to harbor stem cell populations and offer several advantages over more established stem cell sources. Following parturition, the afterbirth is routinely discarded as medical waste, so the isolation of resident stem cell populations doesn’t raise ethical concerns. Harvest is non-invasive and poses no additional risk to the mother or child. Most importantly, stem cells from the afterbirth may be more potent, more proliferative, and less likely to trigger an immune response following transplantation than counterparts isolated from adult tissues.
Our extra-embryonic tissue of choice is the amnion, a flexible and resilient membrane that surrounds the fetus during gestation. Using an explant approach, we have isolated a stem cell population from the rat amnion, called Amnion-derived Stem Cells (ADSCs). These cells are highly proliferative and can be greatly expanded in culture. Under defined conditions ADSCs readily differentiate into in vitro equivalents of mature bone cells and fat cells. Under different conditions, ADSCs acquire characteristics of liver cells and neurons, indicating that they are highly plastic. We are currently assessing the ability of ADSCs to differentiate into additional, clinically relevant cell types, including pancreatic cells for the treatment of diabetes.
Much work remains to determine the role ADSCs and other extra-embryonic stem cells will play in the treatment of disease, but exploitation of stem cells from all available sources is sure to enhance the probability of clinical success. Basic research examining stem cell biology is an important first step on the path to future therapies.
Dale Woodbury earned his Bachelor of Science degree from the University of Connecticut and his PhD from Rutgers University. He has been an assistant professor in the Department of Neuroscience and Cell Biology at UMDNJ-Robert Wood Johnson Medicsl School since 2001 and a member of the Ira B. Black Center for Stem Cell Research since its inception in 2002. Research at the Center has been funded in part by the National Institutes of Health, the New Jersey Commission on Science and Technology, and the Albert Zofchak Fund.
