GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells
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 s...
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doaj-d0c6f8b8ad2a4675ad21598db45837a32020-11-24T23:02:32ZengElsevierStem Cell Reports2213-67112016-02-016224325610.1016/j.stemcr.2015.12.010GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem CellsSaritha S. D'Souza0John Maufort1Akhilesh Kumar2Jiuchun Zhang3Kimberley Smuga-Otto4James A. Thomson5Igor I. Slukvin6National Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USANational Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USANational Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USAMorgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USAMorgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USAMorgridge Institute for Research, 309 North Orchard Street, Madison, WI 53715, USANational Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715, USAAdvances 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.http://www.sciencedirect.com/science/article/pii/S2213671115003756 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saritha S. D'Souza John Maufort Akhilesh Kumar Jiuchun Zhang Kimberley Smuga-Otto James A. Thomson Igor I. Slukvin |
spellingShingle |
Saritha S. D'Souza John Maufort Akhilesh Kumar Jiuchun Zhang Kimberley Smuga-Otto James A. Thomson Igor I. Slukvin GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells Stem Cell Reports |
author_facet |
Saritha S. D'Souza John Maufort Akhilesh Kumar Jiuchun Zhang Kimberley Smuga-Otto James A. Thomson Igor I. Slukvin |
author_sort |
Saritha S. D'Souza |
title |
GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells |
title_short |
GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells |
title_full |
GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells |
title_fullStr |
GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells |
title_full_unstemmed |
GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells |
title_sort |
gsk3β inhibition promotes efficient myeloid and lymphoid hematopoiesis from non-human primate-induced pluripotent stem cells |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2016-02-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671115003756 |
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