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

Shinya Eto,Minami Soga,Yumi Kaneko,Takumi Era,Mizuki Goto,Yusuke Uehara,Hiroshi Mizuta,Johnson Rajasingh

doi:10.1371/journal.pone.0200790

Shinya Eto, Minami Soga + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0200790

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Journal: PloS one	Publication Date: Jul 25, 2018
Citations: 38	License type: CC BY 4.0

Affiliation: Kumamoto University, Oita University

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.

Highlights

Mesenchymal stem cells (MSCs) derived from embryonic mesoderm and neuroepithelium can be cultured in vitro to maintain their multipotency or be differentiated into three principle lineages: adipocyte, chondrocyte, and osteocyte [1,2,3]
The paraxial mesoderm differentiates into mesenchyme descendants such as osteocytes, chondrocytes, and skeletal muscle cells that are MSC progenies; from this, we proposed that human induced pluripotent stem cells (hiPSCs)-derived PDGFRα single positive cell (PSP) could give rise to MSCs
embryoid bodies (EB) were spread on collagen type IV-coated dishes and cultured in the presence of bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor, activin A, and LiCl for 5 days

Summary

Introduction

Mesenchymal stem cells (MSCs) derived from embryonic mesoderm and neuroepithelium can be cultured in vitro to maintain their multipotency or be differentiated into three principle lineages: adipocyte, chondrocyte, and osteocyte [1,2,3]. In human and mouse adults, MSCs can be isolated from bone marrow, adipose tissue, and several other sites such as vascular pericytes [4]. MSCs isolated from adult tissues are valuable cell source for regenerative medicine because of their multipotency [5]. MSCs are used clinically in patients with graft-versushost disease and various inflammatory conditions such as Crohn’s disease because of their modulatory effect on the immune response [6]. Clinical trials far have tested the efficacy of treatments with human MSCs for acute kidney failure, liver fibrosis, tendinitis, juvenile diabetes, radiation syndrome and rheumatoid arthritis, and inflammatory bowel disease [7,8].

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