Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages

Huan-Chin Tseng; Teh-Fu Hsu; Yi-Ying Lin; Wei-Yi Lai; Yu-Hao Liu; Yi-Ping Yang; Cheng-Fong Chen; Chien-Ying Wang

doi:10.1097/JCMA.0000000000001058

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages

J Chin Med Assoc. 2024 Mar 1;87(3):267-272. doi: 10.1097/JCMA.0000000000001058. Epub 2024 Jan 22.

Authors

Huan-Chin Tseng^{1

2}, Teh-Fu Hsu^{3

4}, Yi-Ying Lin^{1

2}, Wei-Yi Lai^{1

2}, Yu-Hao Liu^{1

2}, Yi-Ping Yang^{1

2}, Cheng-Fong Chen^{5

6

7}, Chien-Ying Wang^{1

8

9

7}

Affiliations

¹ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
² Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
³ Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁴ Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
⁵ Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁶ Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
⁷ Department of Exercise and Health Sciences, University of Taipei, Taipei, Taiwan, ROC.
⁸ Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁹ Division of Trauma, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

PMID: 38277620
DOI: 10.1097/JCMA.0000000000001058

Abstract

Background: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs).

Methods: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations.

Results: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential.

Conclusion: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

MeSH terms

Cell Differentiation
Induced Pluripotent Stem Cells*
Mesenchymal Stem Cells*