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

• Published in: Stem cell research & therapy 2017-06, Vol.8 (1), p.143-143, Article 143
• Main Authors: Rengasamy, Mathiyazhagan, Singh, Gurbind, Fakharuzi, Noor Atiqah, Siddikuzzaman, Balasubramanian, Sudha, Swamynathan, Priyanka, Thej, Charan, Sasidharan, Gopinath, Gupta, Pawan Kumar, Das, Anjan Kumar, Rahman, Ahmad Zuhairi Abd, Fakiruddin, Kamal Shaik, Nian, Lim Moon, Zakaria, Zubaidah, Majumdar, Anish S
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Animal models; Animals; Bone marrow; Bone Marrow Transplantation; Carbon Tetrachloride - toxicity; Care and treatment; Cell growth; Clinical trials; Collagen; Disease Models, Animal; Epithelial Cell Adhesion Molecule - genetics; Extracellular matrix; Fibroblasts; Fibrosis; Gastroenterology; Health aspects; Hepatitis; Hepatocytes; Human BM- and WJ-MSCs; Humans; Hydroxyproline; Interstitial collagenase; Liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; Liver Cirrhosis - therapy; Liver diseases; Liver fibrosis; Matrix metalloproteinase; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchyme; Metalloproteinase; Methods; MMPs; Myofibroblasts - metabolism; Neonates; Rats; Stem cell transplantation; Stem cells; Stromal cells; Transplantation; Umbilical cord; Vascular endothelial growth factor; Wharton Jelly - cytology
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0595-1

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 CCl -induced liver fibrosis in rats. Sprague-Dawley rats were injected with CCl 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 × 10 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. 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. Our findings suggest that BM-MSCs are more effective than WJ-MSCs in treating liver fibrosis in a CCl -induced model in rats. The superior therapeutic activity of BM-MSCs may be attributed to their expression of certain MMPs and angiogenic factors.