Surgery
Volume 146, Issue 2 , Pages 190-197, August 2009

Mesenchymal stem cells enhance the viability and proliferation of human fetal intestinal epithelial cells following hypoxic injury via paracrine mechanisms

  • Brent R. Weil, MD

      Affiliations

    • Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
    • ,
  • Troy A. Markel, MD

      Affiliations

    • Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
    • ,
  • Jeremy L. Herrmann, MD

      Affiliations

    • Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
    • ,
  • Aaron M. Abarbanell, MD

      Affiliations

    • Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
    • ,
  • Daniel R. Meldrum, MD

      Affiliations

    • Clarian Cardiovascular Surgery, Indiana University School of Medicine, Indianapolis, IN
    • Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
    • Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN
    • Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN
    • Corresponding Author InformationReprint requests: Daniel R. Meldrum, MD, 635 Barnhill Drive, Van Nuys Medical Science Building, Room 2017, Indianapolis, IN 46202.

Accepted 2 March 2009.

Background

Mesenchymal stem cells (MSCs) may be used to treat injured tissues. The ability of MSCs to treat injured fetal intestinal epithelial cells (FIEs), similar to those in infants with necrotizing enterocolitis, has not been elucidated. We hypothesized that MSCs would enhance FIE viability and proliferation after hypoxic injury via paracrine mechanisms.

Methods

LLC-PK1 cells (differentiated control [DC]) and human MSCs were exposed to 1 hour of hypoxia. Cells were reoxygenated for 24 hours and cell-free conditioned media were collected. Human FIEs were exposed to 1 hour of hypoxia and plated for experiments. FIEs were reoxygenated in nonconditioned media, DC-conditioned media, or MSC-conditioned media. Supernatants were analyzed for interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) via enzyme-linked immunosorbent assay. Cell viability was assessed by trypan blue exclusion and cell counting. Proliferation was determined via 5-bromo-2'-deoxyuridine (BrdU). Expression of caspases-3 and -8 was determined via Western blot.

Results

FIEs reoxygenated in MSC-conditioned media demonstrated enhanced viability and increased proliferation after hypoxic injury. Enhanced FIE viability and proliferation were associated with increased IL-6, HGF, and VEGF, as well as decreased expression of caspase-3.

Conclusion

MSCs may increase the viability and proliferative capacity of FIEs after hypoxic injury via the paracrine release of IL-6, HGF, and VEGF, as well as downregulation of apoptotic signaling.

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 Presented at the 69th Annual Meeting of the Society of University Surgeons, Fort Myers, Florida, February 3–6, 2009.

 Supported in part by research grants from the National Institutes of Health (R01GM070628 [to D.R.M.], R01HL085595 [to D.R.M.], F32HL093987 [to B.R.W.], F32HL085982 [to T.A.M.], F32HL092718 [to A.M.A.], and F32HL092719 [to J.L.H.]).

 B.R.W. and T.A.M. contributed equally to this publication.

PII: S0039-6060(09)00233-5

doi:10.1016/j.surg.2009.03.031

Surgery
Volume 146, Issue 2 , Pages 190-197, August 2009

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