Dr. Peter's Hornsby's lab focus in on nonhuman primate iPS cells in regenerative medicine. Before personalized cell therapy is used in humans, there is need to move beyond rodent models. Beyond rodents, nonhuman primates play key roles in biomedical research. The marmoset is a suitable size and life span for aging studies, and there is the availability of disease models, e.g. Parkinson’s disease, in this species.
A somatic cell type, such as skin fibroblasts, from human patients or from animal models, is reprogrammed to induced pluripotent stem cells. Directed differentiation is used to derive stem/progenitor cells and finally fully differentiated cells in vitro. The diagram illustrates the basic principle underlying protocols that aim for efficient and rational differentiation of pluripotent cells. A typical differentiation protocol goes through multiple stages, attempting to mimic embryonic development by using molecules to stimulate the pathways that are required, while using the same or other molecules to block unwanted differentiation to other pathways at each stage. In this diagram, intermediate cell populations are termed “stem/progenitor cells,” although they may not directly correspond to any population of cells found in actual tissues in vivo, either in the embryo or the adult.
At the end of the process illustrated here, the aim is to have a population of cells that are suitable for cell therapy or for other purposes. The characterization of the differentiated cells in vitro enables the analysis of the phenotype of cells derived from patients with known genetic diseases or genetic changes, and screening for disease mechanisms and small-molecule therapies in cells from such patients. Human cells can be transplanted into model species for various aspects of disease modeling. When cells are derived from model animal species, such as the marmoset illustrated here, they can be transplanted back into the same host species, enabling aspects of disease modeling.
Zhifang Qiu; Anuja
Mishra; Miao Li; Steven L Farnsworth; Bernadette Guerra; Robert E Lanford; Peter J
pluripotent stem cells: Robust neural differentiation following pretreatment
with dimethyl sulfoxide. Journal: Stem Cell
Mishra A, Qui Z, Farnsworth SL, Hemmi JJ, Li M, Pickering AV, Hornsby PJ. Induced Pluripotent Stem Cells from Nonhuman Primates. Methods Mol Biol 201 Dec 26. 2016;1357:183-93.
Qiu Z, Farnsworth SL, Mishra A, Hornsby PJ. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models. Stem Cells Cloning. 2013 Jul 3;6:19-29.
Farnsworth SL, Qiu Z, Mishra A, Hornsby PJ. Directed neural differentiation of induced pluripotent stem cells from non-human primates. Exp Biol Med (Maywood). 2013 Mar;238(3):276-84.
Wu Y, Zhang Y, Mishra A, Tardif SD, Hornsby PJ. Generation of induced pluripotent stem cells from newborn marmoset skin fibroblasts. Stem Cell Res. 2010 May;4(3):180-8.