No potential therapy for neurodegenerative conditions has provoked emotional extremes so positive and so negative as stem cell transplantation (SCT). Hematopoietic SCT, which involves transplantation of stem cells derived from bone marrow or blood, is one of several approaches being investigated for a variety of neurodegenerative diseases, specifically multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease.

Unlike most peripheral tissues, which have at least some ability to self-repair, the central nervous system (CNS) is relatively resistant to regeneration.¹ Within the past few decades, therefore, a great deal of interest has centered on the possibility of repairing damaged tissue in patients with neurodegenerative diseases by introducing healthy new cells from exogenous or endogenous sources.¹ Interest has primarily centered on stem cells, which are undifferentiated cells capable of proliferation and differentiation into cells committed to specific developmental pathways.^2-4 In addition to the potential for replacing injured neurons, stem cells appear to exert beneficial effects through mechanisms unrelated to differentiation (such as secretion of trophic factors, promotion of regrowth of damaged axons, and stimulation of endogenous stem cells in the diseased host brain).¹ One of many challenges has been the identification of a renewable source of stem cells appropriate for wide-scale use.¹ Overcoming this obstacle will be a key to making stem cell transplantation (SCT) a realistic clinical option for patients with conditions such as Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), as well as stroke, injuries to the spinal cord, and brain injuries.

A wide range of stem cells have been investigated as possible sources for transplantation in patients with neurodegenerative diseases (Table). At this time, it remains unclear which types of stem cells might offer the best approach to the treatment of specific disorders.⁵

Embryonic stem cells (ESCs) are derived from the inner cell mass of blastocysts, are pluripotent (capable of differentiating into all cell types, except placental cells), and have the ability to renew themselves.^1,5 Currently available ESC lines originated from embryos that were generated for in vitro fertilization (and would otherwise have been destroyed), with the informed consent of the donors.⁶ Prior to transplantation, ESCs must be differentiated—that is, directed toward development into a particular cell type.^1,6 Several successful protocols have been devised for this purpose, although the extent to which cells should be differentiated remains a matter of debate owing to certain risks.⁶ Because of their pluripotentiality, ESCs can form teratomas (benign tumors containing multiple lineages) or unwanted cell types (for example, changing into bone or muscle when transplanted into the brain) if even a single undifferentiated cell is present in a differentiated transplant.⁶ These concerns must be balanced against the fact that greater degrees of differentiation are accompanied by reductions in proliferative capacity.⁶ Partial differentiation of ESCs into a progenitor cell population prior to transplantation has been suggested as a way of reducing the risks of teratoma and random differentiation while maintaining proliferative ability.⁶

A promising alternative method of securing neurons for the repair of brain damage would be to harvest stemlike progenitor cells from adult tissue.¹ Adult stem cells tend to be self-renewing and tissue specific, capable of differentiating into cell types associated with the organ systems in which they reside.^7,8 In effect, such cells that come from the nervous system are already “neurally specified,” so they do not need to be directed toward a neural lineage, as in the case of pluripotent cells such as ESCs.¹ Another advantage of adult stem cells is that they could be used in autologous therapy, thereby avoiding the risk of immune rejection.^2,9

Adult bone marrow contains 2 major stem cell populations that have been evaluated for transplantation: mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs). Bone marrow–derived adult MSCs (also known as multipotent adult progenitor cells) are relatively easy to isolate, and their numbers can be multiplied in vitro for transplantation.¹ These cells have the capability of differentiating into numerous tissue types.⁹ Furthermore, bone marrow MSCs have been used for many years to treat hematopoietic diseases, so protocols regarding their acquisition and application are well established.¹ Studies of HSCs have suggested that their transdifferentiation into neurons is rare in the intact adult brain but can be induced by a specific microenvironment in injured tissues.²