GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells.

TitleGSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells.
Publication TypeJournal Article
Year of Publication2016
AuthorsD'Souza SS, Maufort J, Kumar A, Zhang J, Smuga-Otto K, Thomson JA, Slukvin II
JournalStem Cell Reports
Volume6
Issue2
Pagination243-56
Date Published2016 Feb 9
ISSN2213-6711
Abstract

Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs) open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP) models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3β inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model.

DOI10.1016/j.stemcr.2015.12.010
Alternate JournalStem Cell Reports
PubMed ID26805448
PubMed Central IDPMC4750098
Grant ListP51 OD011106 / OD / NIH HHS / United States
U01 HL099773 / HL / NHLBI NIH HHS / United States
UL1 TR000427 / TR / NCATS NIH HHS / United States