Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells

Ross A. Kopher; Vesselin R. Penchev; Mohammad S. Islam; Katherine L. Hill; Sundeep Khosla; Dan S. Kaufman

doi:10.1016/j.bone.2010.06.020

Human embryonic stem cell-derived CD34⁺ cells function as MSC progenitor cells

Ross A. Kopher, Vesselin R. Penchev, Mohammad S. Islam, Katherine L. Hill, Sundeep Khosla, Dan S. Kaufman

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73⁺ cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34⁺CD73^- cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34⁺CD73^- cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.

Original language	English (US)
Pages (from-to)	718-728
Number of pages	11
Journal	Bone
Volume	47
Issue number	4
DOIs	https://doi.org/10.1016/j.bone.2010.06.020
State	Published - Oct 2010

Bibliographical note

Funding Information:
We would like to thank Dr. Genya Gekker for her assistance in the operation and data analysis for flow cytometry and sorting. We would like to thank the Masonic Cancer Center Pathology Shared Resource at the University of Minnesota for explant processing and histology. We would also like to thank Jeremy Allred and Dr. Anita Undale for their technical assistance. This project was supported by NIH/NHLBI R01-HL77923 (D.S.K.), a University of Minnesota–Mayo Clinic Collaborative Grant (D.S.K. and S.K.), and the Minnesota Craniofacial Research Training Program (R.A.K.). The project described was supported by Grant Numbers T32DE007288 and F32DE020976 from the National Institute of Dental and Craniofacial Research . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Dental and Craniofacial Research or the National Institutes of Health.

Keywords

Differentiation
Hematopoietic stem cells
Human embryonic stem cells
Mesenchymal stem cells
Progenitor cells

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10.1016/j.bone.2010.06.020

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title = "Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells",

abstract = "Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73+ cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34+CD73- cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34+CD73- cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.",

keywords = "Differentiation, Hematopoietic stem cells, Human embryonic stem cells, Mesenchymal stem cells, Progenitor cells",

author = "Kopher, {Ross A.} and Penchev, {Vesselin R.} and Islam, {Mohammad S.} and Hill, {Katherine L.} and Sundeep Khosla and Kaufman, {Dan S.}",

note = "Funding Information: We would like to thank Dr. Genya Gekker for her assistance in the operation and data analysis for flow cytometry and sorting. We would like to thank the Masonic Cancer Center Pathology Shared Resource at the University of Minnesota for explant processing and histology. We would also like to thank Jeremy Allred and Dr. Anita Undale for their technical assistance. This project was supported by NIH/NHLBI R01-HL77923 (D.S.K.), a University of Minnesota–Mayo Clinic Collaborative Grant (D.S.K. and S.K.), and the Minnesota Craniofacial Research Training Program (R.A.K.). The project described was supported by Grant Numbers T32DE007288 and F32DE020976 from the National Institute of Dental and Craniofacial Research . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Dental and Craniofacial Research or the National Institutes of Health.",

year = "2010",

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doi = "10.1016/j.bone.2010.06.020",

language = "English (US)",

volume = "47",

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T1 - Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells

AU - Kopher, Ross A.

AU - Penchev, Vesselin R.

AU - Islam, Mohammad S.

AU - Hill, Katherine L.

AU - Khosla, Sundeep

AU - Kaufman, Dan S.

N1 - Funding Information: We would like to thank Dr. Genya Gekker for her assistance in the operation and data analysis for flow cytometry and sorting. We would like to thank the Masonic Cancer Center Pathology Shared Resource at the University of Minnesota for explant processing and histology. We would also like to thank Jeremy Allred and Dr. Anita Undale for their technical assistance. This project was supported by NIH/NHLBI R01-HL77923 (D.S.K.), a University of Minnesota–Mayo Clinic Collaborative Grant (D.S.K. and S.K.), and the Minnesota Craniofacial Research Training Program (R.A.K.). The project described was supported by Grant Numbers T32DE007288 and F32DE020976 from the National Institute of Dental and Craniofacial Research . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Dental and Craniofacial Research or the National Institutes of Health.

PY - 2010/10

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N2 - Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73+ cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34+CD73- cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34+CD73- cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.

AB - Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73+ cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34+CD73- cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34+CD73- cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.

KW - Differentiation

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