Use of Bone Marrow Stem Cells as Therapy for Behavioral Deficits in Rodent Models of Huntington’s Disease

Abstract

This chapter focuses on three new studies that used autologous (i.e., when the donor and recipient are the same individual) and heterologous (i.e., when the donor and recipient are different individuals) transplants of adult, bone-marrow-derived stem cells to counteract the behavioral deficits produced by intrastriatal injections of quinolinic acid (QA) in rats, a rodent model for Huntington’s disease (HD). These studies support previous findings that have demonstrated that transplants of adult bone-marrow-derived stem cells can survive and integrate into the host tissue and can counteract functional deficits caused by CNS damage. In the initial study using this HD model, nestin-positive cells were observed 14 d after the transplant and GAD-positive cells were observed at 21 d posttransplant, a finding that supports the contention that adult bone-marrow stem cells possess the plasticity to transdifferentiate into neurons. However, because less than 1% of the cells expressed neuronal phenotypes, and because the functional recovery observed in all three studies occurred within 1 mo after transplantation, it is hypothesized that the ameliorative effects of the transplants were due to the production of neurotrophic factors that facilitated functioning of spared neurons, rather than through the replacement of lost neurons. When compared with transplants of heterologous stem cells, the transplants of autologous stem cells were more efficacious, at least for reducing QA-induced behavioral deficits. Because the use of autologous transplants in HD may prove unfeasible, if the mutant gene becomes expressed in the transplanted autologous stem cells, it may become critically important to find ways to reduce any adverse immunological response or other factors that may be limiting the efficacy of heterologous transplants, if this form of therapy is to become clinically viable for HD. In summary, the findings reported in this chapter support the contention that transplantation of adult, bone-marrow-derived stem cells has significant therapeutic potential as a treatment for HD, but research into how to prevent a possible immune reaction of the heterologous transplant may prove to be critical before this approach has clinical utility.