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Review
. 2018 Feb;54(1):37-44.
doi: 10.1016/j.jdsr.2017.10.001. Epub 2017 Nov 9.

Two Novel Mechanisms for Maintenance of Stemness in Mesenchymal Stem Cells: SCRG1/BST1 Axis and Cell-Cell Adhesion Through N-cadherin

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Free PMC article
Review

Two Novel Mechanisms for Maintenance of Stemness in Mesenchymal Stem Cells: SCRG1/BST1 Axis and Cell-Cell Adhesion Through N-cadherin

Naoyuki Chosa et al. Jpn Dent Sci Rev. .
Free PMC article

Abstract

Mesenchymal stem cells (MSCs) retain the ability to self-renew and differentiate into mesenchymal cells. Therefore, human MSCs are suitable candidates for use in regenerative medicine and cell therapies. Upon activation by tissue damage, MSCs contribute to tissue repair through a multitude of processes such as self-renewal, migration, and differentiation. However, loss of self-renewal and multi-lineage differentiation potential occurs at a high rate during cell doubling. Effective MSC therapies require the establishment of new techniques that preserve MSC multipotency after lengthy cell expansions. Here, two novel mechanisms are described for maintenance of stemness in MSCs via scrapie responsive gene 1 (SCRG1)/bone marrow stromal cell antigen-1 (BST1) ligand-receptor combination and cell-cell adhesion through N-cadherin. These two mechanisms findings provide a valuable tool for regenerative medicine and cell therapeutic methods that require the ex vivo expansion of human MSCs while maintaining native stem cell potential.

Keywords: CD106/VCAM1; CD271/LNGFR; Mesenchymal stem cells; N-cadherin; SCRG1/BST1 axis; Stemness.

Figures

Figure 1
Figure 1
Proposed molecular mechanism for maintenance of stemness by the novel ligand–receptor combination SCRG1/BST1. SCRG1 is hypothesized to be secreted into the extracellular space by MSCs and to have autocrine/paracrine activity. The putative receptor for SCRG1 is a complex of BST1 and integrin β1 on the MSC cell surface. The SCRG1/BST1 axis promotes MSC migration and suppresses osteogenic differentiation through the FAK/PI3K/Akt signaling pathway. SCRG1/BST1 maintains the stemness of MSCs and CD271 expression.
Figure 2
Figure 2
Proposed molecular mechanism for maintenance of MSC stemness by cell–cell adhesion through cadherin. The expression of CD106 in MSCs is dependent on cell density and increases via activation of the NF-κB pathway by cell–cell adhesion with N-cadherin in cultures with high cell densities. The phosphorylation of Src kinase through the intracellular domain of N-cadherin plays an important role in the upregulation of CD106. In the MSC intracellular signaling pathway, Src tyrosine kinase and PDGFRβ are ligand-independently activated by N-cadherin through cell–cell adhesion.
Figure 3
Figure 3
The clinical use of MSCs derived from various tissues depends on obtaining sufficient cell populations for transplantation through ex vivo expansion. During long-term in vitro culture of MSCs, stemness can be maintained by the addition and/or overexpression of SCRG1 and the promotion of cell–cell adhesion.

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