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Fetal sheep support the development of hematopoietic cells in vivo from human induced pluripotent stem cells
- Source :
- Experimental hematology. 95
- Publication Year :
- 2020
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Cell type
Hemangioblasts
Induced Pluripotent Stem Cells
Bone Marrow Cells
Biology
Colony-Forming Units Assay
03 medical and health sciences
0302 clinical medicine
Species Specificity
In vivo
Cell Movement
Pregnancy
Genetics
medicine
Animals
Humans
Cell Lineage
Progenitor cell
Induced pluripotent stem cell
Molecular Biology
Fetus
Sheep
Graft Survival
Cell Differentiation
Cell Biology
Hematology
Hematopoietic Stem Cells
In vitro
Lymphocyte Subsets
Cell biology
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Cellular Microenvironment
Genetic Techniques
Liver
030220 oncology & carcinogenesis
Heterografts
Leukocyte Common Antigens
Female
Bone marrow
Cord Blood Stem Cell Transplantation
Subjects
Details
- ISSN :
- 18732399
- Volume :
- 95
- Database :
- OpenAIRE
- Journal :
- Experimental hematology
- Accession number :
- edsair.doi.dedup.....ef0670bcd0950f59e9dd225967dd0ba8