Nonhuman primate embryonic stem cells as a preclinical model for hematopoietic and vascular repair

Abstract

Stem cell-based regenerative medicine therapies have been touted recently as a novel therapeutic approach to treat and cure a wide range of diseases. Both adult and embryonic stem (ES) cells can serve as important sources of precursor cells to derive more mature cells potentially utilized for clinical applications. Nonhuman primates have proven useful as a preclinical model, as demonstrated in studies of hematopoietic cell transplantation, gene therapy, and other areas. The derivation of nonhuman primate ES cells now provides an optimal resource to characterize and test ES cell-based therapies prior to trials with human ES cells. This review describes work to define strategies and mechanisms to derive blood and endothelial cells from nonhuman primate ES cells isolated from various species. Preclinical testing that solely relies on studies of putative therapeutic cells derived from mouse ES cells transplanted into other mice, or analyses of human ES cell-derived cells transplanted into immunodeficient or immunosuppressed rodents may not be predictive of efficacy in subsequent human trials. However, future testing using nonhuman primate ES cell-derived therapeutic cells done as an allogeneic transplant may best predict success for subsequent studies using human ES cells. Therefore, additional research on nonhuman primate ES cells, in addition to work on mouse and human ES cells, is greatly needed to facilitate clinical translation of new stem cell treatments.