Recent Developments in Stem Cell Research and Therapy

Research using human and animal stem cellsi is an extremely active area of current biomedical inquiry. It is contributing new knowledge about the pathways of normal and abnormal cell differentiation and organismal development. It is opening vistas of new cell transplantation therapies for human diseases. Although the availability of a variety of human stem cells is relatively recent—the isolation of human embryonic stem cells was first reported only in 1998—much is happening in both publicly funded and privately funded research centers around the world. It is difficult for anyone to stay abreast of all the results now rapidly accumulating.To help us fulfill our mandate to “monitor stem cell research,” the President’s Council on Bioethics asked several experts to survey the recent published scientific literature and to contribute articles on various areas of stem cell research to this report (see articles by Drs. Gearhart,1 Ludwig and Thomson,2 Verfaillie,3 Prentice,4 Itescu5, 6 and Jaenisch7 in the Appendices). These reviews and the present chapter emphasize peer-reviewed, published work with human stem cells through July 2003. Interested readers should also consult the wide variety of other review articles that have appeared.8This chapter should be read in conjunction with the commissioned review articles cited above. It draws on their findings, as well as on the Council’s own monitoring activities, but it makes no attempt to summarize all the complexity of stem cell research or the vast array of results. Rather we offer here some general observations and specific examples that might help non-scientist readers understand the overall state of present human stem cell research, its therapeutic promise, and some of the problems that need to be solved if the research is to yield sound knowledge and clinical benefit. To that end, we highlight the importance of well-characterized, stable preparations of stem cells for obtaining reproducible experimental results, and we identify several problems that must be solved before these requirements can be fully met. This chapter then describes, by way of illustration and example, some of the better-characterized adult and embryonic stem cells. It also indicates some of the specific investigations that are being conducted with their aid. Finally, it considers how human stem cells are being used to explore their potential for treating disease, using experiments in animal models of Type-1 diabetes as an example, and it points out some of the difficulties that must be overcome before stem cell-based remedies may be available to treat human diseases.We confine our attention here to newly identified types of human stem cells and their potential use in research and future medical treatment. Accordingly, we do not consider those stem cell types that are already well established in medical practice and research. Specifically, we will not examine those preparations of bone marrow cells that have been clinically used for some years to treat various forms of anemia and cancer.9 Neither will we deal with hematopoietic (blood-forming) stem cells that have been isolated and purified from bone marrow and are now being intensively studied.10 Although these developments lie beyond the scope of this report, the demonstrated usefulness of these cells for research and therapy encourages many researchers to expect similar benefits from the newer stem cells that we shall consider here.
I. Stem Cells and Their Derivatives
The adult human body, and all its differentiated cells, tissues, and organs, arise from a small group of cells contained within the early embryo at the blastocyst stage of its development. During in vivo embryonic development, these cells, constituting the inner cell mass (ICM), will divide and differentiate in concert with each other and with the whole of which they are a part, eventually producing the specialized and integrated tissues and organs of the body. But when embryos are grown [using in vitro fertilization (IVF)] in a laboratory setting, these ICM cells may be removed and isolated, and under appropriate conditions some will proliferate in vitro and become embryonic stem cell lines. These embryonic stem cells are capable of becoming many different types of differentiated cells if stimulated to do so in vitro [see endnote 2 for references]. However, it is not yet clear that the cells that survive the in vitro selection process to become embryonic stem cells have all of the same biological properties and potentials as the ICM cells of the blastocyst.7 In particular, it is not known for certain that human embryonic stem cells in vitro can give rise to all the different cell types of the adult body.iiAs noted in the Introduction to this report, stem cells are a diverse class of cells, which can now be isolated from a variety of embryonic, fetal, and adult tissues. Stem cells share two characteristic properties: (1) unlimited or prolonged self-renewal (that is, the capacity to maintain a pool of stem cells like themselves), and (2) potency for differentiation, the potential to produce more differentiated cell types—usually more than one and, in some cases, many.iii
When stem cells head down the pathway toward differentiation, they usually proceed by first giving rise to a more specialized kind of stem cell (sometimes called “precursor cells” or “progenitor cells”), which can in turn either proliferate through self-renewal or produce fully specialized or differentiated cells