RRC ID 68131
Author Abe T, Uosaki H, Shibata H, Hara H, Sarentonglaga B, Nagao Y, Hanazono Y.
Title Fetal sheep support the development of hematopoietic cells in vivo from human induced pluripotent stem cells.
Journal Exp Hematol
Abstract We report that a sheep fetal liver provides a microenvironment for generating hematopoietic cells with long-term engrafting capacity and multilineage differentiation potential from human induced pluripotent stem cell (iPSC)-derived hemogenic endothelial cells (HEs). Despite the promise of iPSCs for making any cell types, generating hematopoietic stem and progenitor cells (HSPCs) is still a challenge. We hypothesized that the hematopoietic microenvironment, which exists in fetal liver but is lacking in vitro, turns iPSC-HEs into HSPCs. To test this, we transplanted CD45-negative iPSC-HEs into fetal sheep liver, in which HSPCs first grow. Within 2 months, the transplanted cells became CD45 positive and differentiated into multilineage blood cells in the fetal liver. Then, CD45-positive cells translocated to the bone marrow and were maintained there for 3 years with the capability of multilineage differentiation, indicating that hematopoietic cells with long-term engraftment potential were generated. Moreover, human hematopoietic cells were temporally enriched by xenogeneic donor-lymphocyte infusion into the sheep. This study could serve as a foundation to generate HSPCs from iPSCs.
Volume 95
Pages 46-57.e8
Published 2021-3-1
DOI 10.1016/j.exphem.2020.12.006
PII S0301-472X(20)30695-0
PMID 33395577
MeSH Animals Bone Marrow Cells / cytology Cell Differentiation Cell Lineage Cell Movement Cellular Microenvironment Colony-Forming Units Assay Cord Blood Stem Cell Transplantation Female Genetic Techniques Graft Survival Hemangioblasts / cytology Hematopoietic Stem Cells / cytology* Heterografts Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / transplantation* Leukocyte Common Antigens / analysis Liver / embryology Lymphocyte Subsets Pregnancy Sheep / embryology* Species Specificity
IF 2.82
Human and Animal Cells 409B2(HPS0076) 454E2(HPS0077)