Stem Cell Research & Therapy (Jun 2017)

Transplantation of human bone marrow mesenchymal stromal cells reduces liver fibrosis more effectively than Wharton’s jelly mesenchymal stromal cells

  • Mathiyazhagan Rengasamy,
  • Gurbind Singh,
  • Noor Atiqah Fakharuzi,
  • Siddikuzzaman,
  • Sudha Balasubramanian,
  • Priyanka Swamynathan,
  • Charan Thej,
  • Gopinath Sasidharan,
  • Pawan Kumar Gupta,
  • Anjan Kumar Das,
  • Ahmad Zuhairi Abd Rahman,
  • Kamal Shaik Fakiruddin,
  • Lim Moon Nian,
  • Zubaidah Zakaria,
  • Anish S. Majumdar

DOI
https://doi.org/10.1186/s13287-017-0595-1
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract Background Mesenchymal stromal cells (MSCs) from various tissues have shown moderate therapeutic efficacy in reversing liver fibrosis in preclinical models. Here, we compared the relative therapeutic potential of pooled, adult human bone marrow (BM)- and neonatal Wharton’s jelly (WJ)-derived MSCs to treat CCl4-induced liver fibrosis in rats. Methods Sprague-Dawley rats were injected with CCl4 for 8 weeks to induce irreversible liver fibrosis. Ex-vivo expanded, pooled human MSCs obtained from BM and WJ were intravenously administered into rats with liver fibrosis at a dose of 10 × 106 cells/animal. Sham control and vehicle-treated animals served as negative and disease controls, respectively. The animals were sacrificed at 30 and 70 days after cell transplantation and hepatic-hydroxyproline content, histopathological, and immunohistochemical analyses were performed. Results BM-MSCs treatment showed a marked reduction in liver fibrosis as determined by Masson’s trichrome and Sirius red staining as compared to those treated with the vehicle. Furthermore, hepatic-hydroxyproline content and percentage collagen proportionate area were found to be significantly lower in the BM-MSCs-treated group. In contrast, WJ-MSCs treatment showed less reduction of fibrosis at both time points. Immunohistochemical analysis of BM-MSCs-treated liver samples showed a reduction in α-SMA+ myofibroblasts and increased number of EpCAM+ hepatic progenitor cells, along with Ki-67+ and human matrix metalloprotease-1+ (MMP-1+) cells as compared to WJ-MSCs-treated rat livers. Conclusions Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl4-induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.

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