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NOTCH Activation at the Hematovascular Mesoderm Stage Facilitates Efficient Generation of T Cells with High Proliferation Potential from Human Pluripotent Stem Cells
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 202(3)
- Publication Year :
- 2018
-
Abstract
- Human pluripotent stem cells (hPSCs) offer the potential to serve as a versatile and scalable source of T cells for immunotherapies, which could be coupled with genetic engineering technologies to meet specific clinical needs. To improve T cell production from hPSCs, it is essential to identify cell subsets that are highly enriched in T cell progenitors and those stages of development at which NOTCH activation induces the most potent T cells. In this study, we evaluated the efficacy of T cell production from cell populations isolated at different stages of hematopoietic differentiation, including mesoderm, hemogenic endothelium (HE), and multipotent hematopoietic progenitors. We demonstrate that KDRhiCD31− hematovascular mesodermal progenitors (HVMPs) with definitive hematopoietic potential produce the highest numbers of T cells when cultured on OP9-DLL4 as compared with downstream progenitors, including HE and multipotent hematopoietic progenitors. In addition, we found that T cells generated from HVMPs have the capacity to expand for 6–7 wk in vitro, in comparison with T cells generated from HE and hematopoietic progenitors, which could only be expanded for 4–5 wk. Demonstrating the critical need of NOTCH activation at the HVMP stage of hematopoietic development to establish robust T cell production from hPSCs may aid in establishing protocols for the efficient off-the-shelf production and expansion of T cells for treating hematologic malignancies.
- Subjects :
- 0301 basic medicine
Pluripotent Stem Cells
Mesoderm
T cell
T-Lymphocytes
Immunology
Biology
Article
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Immunology and Allergy
Animals
Humans
Lymphopoiesis
Progenitor cell
Receptor, Notch1
Induced pluripotent stem cell
Cell Proliferation
Hemogenic endothelium
Cell growth
Fibroblasts
Flow Cytometry
Coculture Techniques
Cell biology
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 202
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....af7f929949065901a056e0135f76bd77