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Living scaffolds: surgical repair using scaffolds seeded with human adipose-derived stem cells

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Abstract

Background

Decellularized porcine small intestinal submucosa (SIS) is a biological scaffold used surgically for tissue repair. Here, we demonstrate a model of SIS as a scaffold for human adipose-derived stem cells (ASCs) in vitro and apply it in vivo in a rat ventral hernia repair model.

Study design

ASCs adherence was examined by confocal microscopy and proliferation rate was measured by growth curves. Multipotency of ASCs seeded onto SIS was tested using adipogenic, chondrogenic, and osteogenic induction media. For in vivo testing, midline abdominal musculofascial and peritoneal defects were created in Sprague–Dawley rats. Samples were evaluated for tensile strength, histopathology and immunohistochemistry.

Results

All test groups showed cell adherence and proliferation on SIS. Fibronectin-treated scaffolds retained more cells than those treated with vehicle alone (p < 0.05). Fresh stromal vascular fraction (SVF) pellets containing ASCs were injected onto the SIS scaffold and showed similar results to cultured ASCs. Maintenance of multipotency on SIS was confirmed by lineage-specific markers and dyes. Histopathology revealed neovascularization and cell influx to ASC-seeded SIS samples following animal implantation. ASC-seeded SIS appeared to offer a stronger repair than plain SIS, but these results were not statistically significant. Immunohistochemistry showed continued presence of cells of human origin in ASC-seeded repairs at 1 month postoperation.

Conclusion

Pretreatment of the scaffold with fibronectin offers a method to increase cell adhesion and delivery. ASCs maintain their immunophenotype and ability to differentiate while on SIS. Seeding freshly isolated SVF onto the scaffold demonstrated that minimally manipulated cells may be useful for perioperative surgical applications within the OR suite. We have shown that this model for a “living mesh” can be successfully used in abdominal wall reconstruction.

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Abbreviations

SIS:

Small intestinal submucosa

hASCs:

Human adipose-derived stem cells

SVF:

Stromal vascular fraction

FN:

Fibronectin

CDT:

Cell doubling time

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Acknowledgments

Support for this study was provided in part by NIH grant R01HL073980 (TNT) and DOD contract W81XW H08-2-00 (TNT). Biodesign was a kind gift of Cook Biotech (West Lafayette, IN).

Author information

Authors and Affiliations

  1. Department of Surgery, Cooper University Hospital and Cooper Medical School at Rowan University, 3 Cooper Plaza, Camden, NJ, 08108, USA

    A. Klinger, M. Kawata, M. Villalobos, R. B. Jones, S. Pike, N. Wu, S. Chang, P. Zhang, R. D. Goldfarb, K. Hunter, Y. Liu, J. P. Carpenter & T. N. Tulenko

  2. Department of Medicine, Cooper University Hospital and Cooper Medical School at Rowan University, Camden, NJ, USA

    A. Klinger, M. Kawata, M. Villalobos, R. B. Jones, S. Pike, N. Wu, S. Chang, P. Zhang, R. D. Goldfarb, K. Hunter, Y. Liu & J. P. Carpenter

  3. Department of Chemical Engineering, Rowan University, 201 Mullica Hill Road, Glassboro, NJ, 08028, USA

    J. Vernengo & P. Benvenuto

  4. Department of Surgery, Thomas Jefferson University, 1020 Walnut Street, Philadelphia, PA, 19107, USA

    P. DiMuzio

Authors
  1. A. Klinger
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  2. M. Kawata
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  3. M. Villalobos
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  4. R. B. Jones
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  5. S. Pike
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  6. N. Wu
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  7. S. Chang
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  8. P. Zhang
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  9. P. DiMuzio
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  10. J. Vernengo
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  11. P. Benvenuto
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  12. R. D. Goldfarb
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  13. K. Hunter
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  14. Y. Liu
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  15. J. P. Carpenter
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  16. T. N. Tulenko
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Corresponding author

Correspondence to T. N. Tulenko.

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Klinger, A., Kawata, M., Villalobos, M. et al. Living scaffolds: surgical repair using scaffolds seeded with human adipose-derived stem cells. Hernia 20, 161–170 (2016). https://doi.org/10.1007/s10029-015-1415-0

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  • DOI: https://doi.org/10.1007/s10029-015-1415-0

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