NIH CRM supported pilot projects in 13 laboratories, representing the following institutes: NIAID, NIAMS, NICHD, NIDDK, NEI, NHGRI, NHLBI, NIEHS, and NINDS. The projects focus on iPSCs yet cover a broad range of topics. Of the 13 NIH CRM funded projects, 6 propose to generate iPSC-based disease models. Two of these projects plan to develop models of diseases associated with retinal degeneration, one of Age-related Macular Degeneration (AMD) and the other of Leber Congenital Amaurosis (LCA). 3 projects focused on neurological disease models, specifically Spinal Bulbar Muscular Atrophy (SBMA) and Amyotrophic lateral sclerosis (ALS), Smith-Lemli-Opitz Syndrome (SLOS), and Gauchers disease. The last iPSC-based disease model project proposes to study telomere biology in the context of iPSCs. They will generate iPSCs from Aplastic Anemia (AA) patients in order to and analyze the mechanisms of telomere elongation during iPSC generation. The next 3 projects study the effects of different factors on cellular reprogramming and differentiation. One of these projects aims to improve the efficiency of ESC/iPSC commitment and differentiation by studying the role of Polycomb group proteins on epigenetic regulation. Another project addresses the role of STAT3 in iPSC reprogramming and differentiation into cells of mesodermal lineages. The third project examines the role of GLIS3 in the differentiation of iPSCs into pancreatic beta cells. The next 3 projects use genetic engineering of iPSCs to develop cell-based therapies. In one of these projects the investigators propose to make iPSCs from Chronic Granulomatous Disease patients, then genetically correct them using ZFN technology, and finally differentiate them into neutrophils and/or Hematopoietic Stem Cells (HSCs) for patient transfusion. Another project aims to treat alpha-1-antitrypin (AAT) deficiency using the same ZFN technology, differentiate the cells to hepatocytes, and analyzing the effect on disease correction in vitro. The third project proposes to stimulate anti-glioma immune responses using iPSC-derived microglia. They will test the ability of the iPSC-derived microglia to impact tumor growth using a mouse model of glioblastoma. The final project aims to develop the preclinical animal models necessary to perform clinical translation of a cellular therapy. They will generate non-human primate (rhesus) iPSCs to test important aspects of transplantation and teratoma-forming potential of primate pluripotent cells (and their products) in an autologous primate host.
