Int J Stem Cells.  2021 May;14(2):150-167. 10.15283/ijsc20167.

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases

• Chung MJ
• Son JY
• Park S
• Park SS
• Hur K
• Lee SH
• Lee EJ
• Park JK
• Hong IH
• Kim TH
• Jeong KS

• KMID: 2515992
• DOI: http://doi.org/10.15283/ijsc20167

Abstract

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Keyword

Mesenchymal stem cells; Induced pluripotent stem cells; Cell therapy; Musculoskeletal disorder; MicroRNA; Exosome

Figure

• 

  Fig. 1 Process of cell-free therapy from MSCs to target cells. In cell-free therapy, there is a method of transmitting exosome secreted from MSCs to target cells, and a method of selecting specific miRNA in MSCs, then synthesizing it in the formed mimic and delivering it to target cells. A transport is needed to deliver miRNA mimic to target cells in vivo. Generally, viral/non-viral carrier and targeted delivery are used.

• 

  Fig. 2 MSC-secreted miRNA therapy for musculoskeletal diseases. As shown in the figure above, different miRNAs secreted by MSCs act on target cells show a positive effect on musculoskeletal diseases. As shown in table 2, there are many miRNAs related to musculoskeletal diseases. Further, it was confirmed that one miRNA could target different genes in different cells giving different effects.

• 

  Fig. 3 Schematic diagram of cell therapy and cell-free therapy. The schematic diagram demonstrating the cell-therapy and cell-free therapy for musculoskeletal disorders. For cell therapy, tissue-derived MSCs and iPSC-MSCs are applied by direct injection into injured area. A part of injected cells migrates to the damaged region of tissue and participates in proliferation and differentiation while most of the injected cells secrete paracrine factors such as exosomes containing miRNAs to promote a regenerative condition. Cell-free therapy includes exosome therapy and miRNA therapy. Exosome can be obtained in massive quantity from iPSC-MSCs, and synthetic miRNA also can be obtained in vitro.

Reference

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