Mesenchymal stem cells derived from human induced pluripotent stem cells retain adequate osteogenicity and chondrogenicity but less adipogenicity.
BACKGROUND
Previously, we established a simple method for deriving mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (iPSC-MSCs). These iPSC-MSCs were capable of forming osteogenic structures in scaffolds and nanofibers. The objective of this study is to systematically characterize the mesenchymal characteristics of the iPSC-MSCs by comparing them to bone marrow-derived MSCs (BM-MSCs).


METHODS
Two iPSC-MSC lines (named as mRNA-iPSC-MSC-YL001 and lenti-iPSC-MSC-A001) and one BM-MSC line were used for the study. Cell proliferation, presence of mesenchymal surface markers, tri-lineage differentiation capability (osteogenesis, chondrogenesis, adipogenesis), and expression of "stemness" genes were analyzed in these MSC lines.


RESULTS
The iPSC-MSCs were similar to BM-MSCs in terms of cell morphology (fibroblast-like) and surface antigen profile: CD29+, CD44+, CD73+, CD90+, CD105+, CD11b-, CD14-, CD31-, CD34-, CD45- and HLA-DR-. A faster proliferative capability was seen in both iPSC-MSCs lines compared to the BM-MSCs. The iPSC-MSCs showed adequate capacity of osteogenesis and chondrogenesis compared to the BM-MSCs, while less adipogenic potential was found in the iPSC-MSCs. The iPSC-MSCs and the tri-lineage differentiated cells (osteoblasts, chondrocytes, adipocytes) all lack expression of "stemness" genes: OCT4, SOX2, GDF3, CRIPTO, UTF1, DPPA4, DNMT3B, LIN28a, and SAL4.


CONCLUSIONS
The MSCs derived from human iPSCs with our method have advanced proliferation capability and adequate osteogenic and chondrogenic properties compared to BM-MSCs. However, the iPSC-MSCs were less efficient in their adipogenicity, suggesting that further modifications should be applied to our method to derive iPSC-MSCs more closely resembling the naïve BM-MSCs if necessary.
Orthopedic Research Lab, Aarhus University, 8000, Aarhus C, Denmark. KANG.RAN@CLIN.AU.DK.|Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, 210028, China. KANG.RAN@CLIN.AU.DK.
Ran
R
Kang
Department of Biomedicine, the Health Faculty, Aarhus University, 8000, Aarhus C, Denmark. YAZH@BIOMED.AU.DK.
Yan
Y
Zhou
Department of Biomedicine, the Health Faculty, Aarhus University, 8000, Aarhus C, Denmark. SHUANG.TAN@HUM-GEN.AU.DK.|Shenzhen Key Laboratory for Anti-aging and Regenerative Medicine, Health Science Center, Shenzhen University, 518060, Shenzhen, China. SHUANG.TAN@HUM-GEN.AU.DK.
Shuang
S
Tan
Shenzhen Key Laboratory for Anti-aging and Regenerative Medicine, Health Science Center, Shenzhen University, 518060, Shenzhen, China. GQZHOU@SZU.EDU.CN.
Guangqian
G
Zhou
Department of Biomedicine, the Health Faculty, Aarhus University, 8000, Aarhus C, Denmark. AAGAARD@BIOMED.AU.DK.
Lars
L
Aagaard
Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, 210028, China. XIELIN117@126.COM.
Lin
L
Xie
Orthopedic Research Lab, Aarhus University, 8000, Aarhus C, Denmark. CODYBUNG@RM.DK.
Cody
C
Bünger
Department of Biomedicine, the Health Faculty, Aarhus University, 8000, Aarhus C, Denmark. BOLUND@BIOMED.AU.DK.
Lars
L
Bolund
Department of Biomedicine, the Health Faculty, Aarhus University, 8000, Aarhus C, Denmark. ALUN@BIOMED.AU.DK.
Yonglun
Y
Luo
D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D016086:Lentivirus; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology