Stem Cells: Biological Innovation

Discovery of Stem Cells: A Brief History

Stem cells have been found to originate from two broad sources (1) embryonic; and (2) adult (bone marrow via iliac crest or femur harvest, adipose via liposuction, blood via apheresis). Potency was determined as “totipotent” (able to differentiate into just about any cell); or “pluripotent” (able to differentiate into more than one, but not all, cell lines).

With Maksimov proposing the histological existence of stem cells in the early 1900s, Altman/Das proposed neurogenesis in the 1960s (refuting Cajal’s theory of lack of neuronal differentiation). Animal research (Becker/McCulloch/Till) in mice showed self-renewing cells, and in 1968 the first bone marrow transplant between siblings treated SCID. Cord blood hematopoietic stem cells in the late 1970s, mouse embryonic (totipotent) stem cells from the inner mass (10-20 cells, early 1980s), and neural stem cells (1990s), and ultimately Matapurkar (1995) showing human tissue utilization with patented neo-generation such as fallopian tubes and uterus. Shortly thereafter, WARF derived a human embryonic stem cell line, and among other discoveries, stem cells in teeth, gonadal tissue, and with uses such as improving walking in rats with spinal cord injury (via injection of neural stem cells).

Stem Cells: Present-day Status

Among the embryonic or adult stem cells, the embryonic from the inner cell mass are likely to be totipotent, whereas adult stem cells are typically pluripotent; dangers considered in transplanting include formation of the tumor teratoma, and hence no present therapy has been both approved and instituted (despite a spinal cord injury trial being approved, but not carried out by the company) using embryonic stem cells. Cell surface proteins likely indicate differentiation.

Cells have been found to undergo two types of cell division – symmetric (identical daughter cell types with stem cell properties); and asymmetric (one progenitor and one limited self-renewal progenitor cell).

Some concerns involve transplant-related immunosuppression, as well as difficulty transforming to a specific cell type. In addition, tumors are a risk as noted previously; also, cells may be used as a method of early detection of new drug-related toxicity (when evaluated in vitro, for example).

Patenting issues, such as those of Wisconsin Alumni Research Foundation (WARF), have led to challenge from the USPTO and others.

Future Options using Stem Cells

The future holds testing being undertaken for trying a variety of disorders. These include diabetes, wound healing, Parkinson’s disease, ALS, spinal cord injury repair, Alzheimer’s disease, stroke, traumatic brain injury, cancer treatment, Crohn’s disease, learning problems, baldness, and restoring special sensory functions such as hearing and vision, along with cardiac/teeth function.

However, focus must be maintained upon present issues including (1) prevention of causing a tumor; (2) proper ability to influence what cell lines are derived ultimately from a stem cell; (3) lack of immunogenic response for foreign (non-autologous) stem cell transplants; and others.

Controversial positions regarding sources of stem cells, e.g. embryonic, may be able to be overcome by growing cells with greater growth potential via control of surface molecules (in culture).

Recent advances, as reviewed in some works (e.g. Cheshier et al, 2009; Singh et al, 2004) suggest that brain tumor stem cells have different characteristics than normal brain stem cells. This suggests that surgical intervention, in the opinion of Cheshier et al, may be less effective since specific brain tumor stem cells are not necessarily targeted.

Exciting new areas, as noted from the “history” section being continued (and written today), include normal skin cells being reprogrammed to an embryonic state in mice/primate cell line creation, and findings of stem cells in amniotic fluid, liver, human hair, and other tissue. Lymphocyte modification using cord-derived stem cells resulted in improved diabetes control measures. Also, derived stem cells from endangered species may be promising for the future. Finally, “3-D printers of stem cells” resulting in clusters of embryonic stem cells (Scotland’s Heriot-Watt University) may allow complete organs to be printed in the future (!)…

(Portions of this text are from sources of the internet, which may include and Cheshier SH et al, Neurosurgery 65:237-250, 2009; Singh SK et al, Nature 432:396-401, 2004)