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Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

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Abstract

Purpose

Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as “fatty degeneration.” As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular fraction stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fibre specific force production after chronic rotator cuff tear.

Methods

Chronic supraspinatus tears were induced in adult immunodeficient rats, and repaired one month following tear. Rats received vehicle control, or injections of 3 × 105 or 3 × 106 human SVFCs into supraspinatus muscles.

Results

Two weeks following repair, we detected donor human DNA and protein in SVFC treated muscles. There was a 40 % reduction in fibrosis in the treated groups compared to controls (p = 0.03 for 3 × 105, p = 0.04 for 3 × 106), and no differences between groups for lipid content or force production were observed.

Conclusions

As there has been much interest in the use of stem cell-based therapies in musculoskeletal regenerative medicine, the reduction in fibrosis and trend towards an improvement in single fiber contractility suggest that SVFCs may be beneficial to enhance the treatment and recovery of patients with chronic rotator cuff tears.

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Acknowledgments

This study was funded by the US Army Medical Research and Materiel Command (DOD contract number W81XWH-10-2-0108) and NIH fellowships (F31-AR065931 and F32-AR067086).

Conflicts of interest

Paul E. Kosnik is an employee of Tissue Genesis, Inc., which received funding support from the Department of Defense for this study. The authors otherwise report no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Michigan Institutional Review Board and with the 1964 Helsinki declaration and its later amendments. All procedures performed with animals were in accordance with the ethical standards of the University of Michigan Committee on the Use and Care of Animals.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, MI, 48109-2200, USA

    Jonathan P. Gumucio, Michael D. Flood, Stuart M. Roche, Kristoffer B. Sugg, Asheesh Bedi & Christopher L. Mendias

  2. Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA

    Jonathan P. Gumucio, Kristoffer B. Sugg & Christopher L. Mendias

  3. Department of Surgery, Section of Plastic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA

    Kristoffer B. Sugg & Adeyiza O. Momoh

  4. Tissue Genesis, Inc., Honolulu, HI, USA

    Paul E. Kosnik

Authors
  1. Jonathan P. Gumucio
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  2. Michael D. Flood
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  3. Stuart M. Roche
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  4. Kristoffer B. Sugg
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  6. Paul E. Kosnik
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  7. Asheesh Bedi
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  8. Christopher L. Mendias
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Corresponding author

Correspondence to Christopher L. Mendias.

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Gumucio, J.P., Flood, M.D., Roche, S.M. et al. Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear. International Orthopaedics (SICOT) 40, 759–764 (2016). https://doi.org/10.1007/s00264-015-2937-x

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  • DOI: https://doi.org/10.1007/s00264-015-2937-x

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