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Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential

Gene Therapy volume 30, pages 369–376 (2023)Cite this article

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Abstract

Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.

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Fig. 1: Representative images of calcium deposition/matrix mineralization in transduced and non-transduced cells.

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Additional data are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Jeffrey Boyd and Bernadette Masinsin, from the Flow Cytometry Facility at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, for their technical assistance with flow cytometry.

Funding

This work is supported by NIH Grant ROI R01AR057076 awarded to JRL.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, 2011 Zonal Ave,HMR 702, Los Angeles, CA, 90089, USA

    Kevin Collon, Jennifer A. Bell, Matthew C. Gallo, Stephanie W. Chang, Sofia Bougioukli, Osamu Sugiyama, Jade Tassey, Nathanael Heckmann, Daniel A. Oakes, Donald B. Longjohn, Denis Evseenko & Jay R. Lieberman

  2. Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA

    Roger Hollis & Donald B. Kohn

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  1. Kevin Collon
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Contributions

KC and JAB were responsible for designing the study, data acquisition, interpreting results, and drafting paper. MCG was responsible for statistical analyses, data acquisition, and drafting paper. SWC was responsible for data acquisition and drafting paper. SB was responsible for performing the statistical analysis and drafting paper. OS was responsible for designing the study and data acquisition and drafting paper. JT and DE were responsible for performing and analyzing flow cytometry data and revising paper. NH, DAO, and DBL were responsible for harvesting specimen and revising paper. RH and DBK were responsible for designing the study methodology and revising paper. JRL was responsible for designing the study methodology, interpreting results, drafting and revising paper.

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Correspondence to Kevin Collon.

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Institutional Review Board approval was obtained prior to collection of human tissue.

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Collon, K., Bell, J.A., Gallo, M.C. et al. Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential. Gene Ther 30, 369–376 (2023). https://doi.org/10.1038/s41434-022-00367-w

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