Abstract
Background:
To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient’s bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration.
Methods:
To examine the donor-to-donor variation of TMSCs in potentiating BMC migration, we isolated TMSCs from 25 independent donors. Transcriptome of TMSCs and proteome of conditioned medium derived from TMSC were analyzed.
Results:
Enhanced BMC migration by conditioned medium derived from TMSCs was variable depending on TMSC donor. The TMSCs derived from 25 donors showed distinct expression profiles compared with other cells, including fibroblasts, adipose-derived MSCs and bone marrow–derived MSCs. TMSCs were distributed in two categories: high- and low-efficacy groups for potentiating BMC migration. Transcriptome analysis of TMSCs and proteome profiles of conditioned medium derived from TMSCs revealed higher expression and secretion of matrix metalloproteinase (MMP) 1 in the high-efficacy group. MMP1 knockdown in TMSCs abrogated the supportive efficacy of conditioned medium derived from TMSC cultures in BMC migration.
Conclusion:
These data suggest that secreted MMP1 can be used as a marker to evaluate the efficacy of TMSCs in enhancing BMC migration. Furthermore, the strategy of analyzing transcriptomes and proteomes of the MSCs may be useful to set the standard for donor variation.
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Acknowledgements
This work was supported by National Research Foundation of Korea grants funded by the Korean Government (Ministry of Education, Science and Technology) [NRF-2017R1E1A1A01073021] and by grants from the Health Technology R&D Project (HI18C2392) of the Ministry of Health and Welfare, Republic of Korea.
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The study procedures were approved by the Institutional Review Board of Ewha Womans University Mokdong Hospital (EUMC 2020–02-028), and all the research was performed according to The Code of Ethics of the World Medical Association (Declaration of Helsinki). Informed consent was confirmed by the Institutional Review Board of Ewha Womans University Mokdong Hospital.
All animal experimental procedures were performed after receiving approval by the Animal care and Use Committee of Ewha Womans University, School of Medicine (EWHA MEDIACUC past-031).
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Kim, HY., Yoon, HS., Lee, Y. et al. Matrix Metalloproteinase 1 as a Marker of Tonsil-Derived Mesenchymal Stem Cells to Assess Bone Marrow Cell Migration. Tissue Eng Regen Med 20, 271–284 (2023). https://doi.org/10.1007/s13770-022-00501-0
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DOI: https://doi.org/10.1007/s13770-022-00501-0