Mesenchymal stem cells derived from human iPS cells via mesoderm and neuroepithelium have different features and therapeutic potentials

Shinya Eto; Mizuki Goto; Minami Soga; Yumi Kaneko; Yusuke Uehara; Hiroshi Mizuta; Takumi Era

doi:10.1371/journal.pone.0200790

Mesenchymal stem cells derived from human iPS cells via mesoderm and neuroepithelium have different features and therapeutic potentials

PLoS One. 2018 Jul 25;13(7):e0200790. doi: 10.1371/journal.pone.0200790. eCollection 2018.

Authors

Shinya Eto¹, Mizuki Goto^{1

2}, Minami Soga¹, Yumi Kaneko¹, Yusuke Uehara³, Hiroshi Mizuta³, Takumi Era¹

Affiliations

¹ Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
² Department of Dermatology, Faculty of Medicine, Oita University, Yufu, Japan.
³ Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Mesenchymal stem cells (MSCs) isolated from adult human tissues are capable of proliferating in vitro and maintaining their multipotency, making them attractive cell sources for regenerative medicine. However, the availability and capability of self-renewal under current preparation regimes are limited. Induced pluripotent stem cells (iPSCs) now offer an alternative, similar cell source to MSCs. Herein, we established new methods for differentiating hiPSCs into MSCs via mesoderm-like and neuroepithelium-like cells. Both derived MSC populations exhibited self-renewal and multipotency, as well as therapeutic potential in mouse models of skin wounds, pressure ulcers, and osteoarthritis. Interestingly, the therapeutic effects differ between the two types of MSCs in the disease models, suggesting that the therapeutic effect depends on the cell origin. Our results provide valuable basic insights for the clinical application of such cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / cytology
Animals
Cell Differentiation
Disease Models, Animal
Humans
Induced Pluripotent Stem Cells / cytology*
Male
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / cytology*
Mesoderm / metabolism
Mice
Oligonucleotide Array Sequence Analysis
Osteogenesis
Regenerative Medicine / methods*
Skin / metabolism

Grants and funding

This study was supported, in part, by grants from Japan Society for the Promotion Science (JSPS, URLs: http://www.jsps.go.jp/english/) program on Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation (Grant Number S2803), the Ministry of Health, Labor, and Welfare of Japan (URLs: http://www.mhlw.go.jp/english/), the Japan Agency for Medical Research and Development (A-MED, URLs: https://www.amed.go.jp/en/), Core Research for Evolutional Science and Technology (CREST, URLs: https://www.jst.go.jp/kisoken/crest/en/), Grant-in-Aid for Scientific Research (KAKENHI C, 25505002 and 18K06264, URLs: https://www.jsps.go.jp/english/e-grants/) and the Japan Science and Technology Agency (JST, URLs: https://www.jst.go.jp/EN/). T.E. received all of above grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.