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Phenotypic, trophic, and regenerative properties of mesenchymal stem cells from different osseous tissues

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Abstract

Mesenchymal stem cells (MSCs) have broad-based therapeutic potential in regenerative medicine. However, a major barrier to their clinical utility is that MSCs from different tissues are highly variable in their regenerative properties. In this study, we defined the molecular and phenotypic identities of different MSC populations from different osseous tissue sites of different patients and, additionally, determined their respective regenerative properties. MSCs from 6 patients were isolated from either bone marrow of the iliac crest (BMSCs) or alveolar bone tissue (aBMSCs), and flow cytometry revealed that regardless of the tissue source, MSC immunotypes had the same expression of MSC markers CD73, CD90, and CD105. However, transcriptomic analyses revealed 589 genes differentially expressed (DE) between BMSCs and aBMSCs, including eightfold higher levels of bone morphogenetic protein 4 (BMP-4) in aBMSCs. In striking contrast, gene expression of MSCs derived from the same tissue, but between different patients (i.e., BMSCs to BMSCs, aBMSCs to aBMSCs), showed only 38 DE BMSC genes and 51 DE aBMSC genes. A protein array showed that aBMSC and BMSC produced equivalent levels of angiogenic cytokines; however, when placed in angiogenesis model systems, aBMSCs induced significantly more capillaries in vitro and in vivo. Finally, cell transplantation of MSCS into osseous defects showed that the bone regenerative capacity of aBMSCs was significantly greater than that of BMSCs. This study is the first to link the molecular, phenotypic, and regenerative properties of different MSCs from different patients and provides novel insights toward MSC differences based on the osseous tissue origin.

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Acknowledgements

The authors would like to acknowledge David Adams and staff at the University of Michigan BRCF Flow Cytometry Core, Robert Lyons, staff at the University of Michigan Sequencing Core and Rich McEachin, and staff at the University of Michigan Bioinformatics Core.

Funding

This study was funded by R56-DE21410 from the NIH/NIDCR (awarded to D.K.) and R01-HL085339 from the NIH/NHLBI (awarded to A.J.P.).

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Authors and Affiliations

  1. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA

    Douhong Zou, Chen Cao, Susan A. Tarlé, Tyler Guinn & Darnell Kaigler

  2. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA

    Marina Vigen, Andrew J. Putnam & Darnell Kaigler

Authors
  1. Douhong Zou
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  2. Marina Vigen
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  3. Andrew J. Putnam
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  4. Chen Cao
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  5. Susan A. Tarlé
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  6. Tyler Guinn
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  7. Darnell Kaigler
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Contributions

Douhong Zou: methodology, data curation, writing — original draft, writing — review and editing. Marina Vigen: methodology, data curation, formal analysis, writing — original draft. Andrew J. Putnam: conceptualization, funding acquisition, writing — original draft; writing — review and editing. Chen Cao: methodology; writing — original draft; writing — review and editing. Susan A. Tarlé: methodology, supervision. Tyler Guinn: methodology, data curation. Darnell Kaigler: conceptualization, funding acquisition, formal analysis, validation, writing — original draft; writing — review and editing.

Corresponding author

Correspondence to Darnell Kaigler.

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All human tissues were collected from patients after obtaining informed consent following University of Michigan Institutional Review Board approval (IRB #HUM00034368), and all animal studies were conducted in accordance with University Institutional Animal Care and Use Committee approvals (PRO00009333, PRO00008804).

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The authors declare no competing interests.

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Zou, D., Vigen, M., Putnam, A.J. et al. Phenotypic, trophic, and regenerative properties of mesenchymal stem cells from different osseous tissues. Cell Tissue Res 388, 75–88 (2022). https://doi.org/10.1007/s00441-021-03563-z

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