Anti-fibrotic effect of intravenous umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection in experimental rats induced liver fibrosis

Abstract

Aim To investigate the effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) administration among liver fibrosis experimental rat model via the regulation of angiotensin II type 1 receptor (AT1R) and platelet-derived growth factor-β (PDGF-β) due to their therapeutic potential to replace liver transplantation for advanced liver fibrosis. Yet the mechanism of action has been questionably associated with UC-MSCs fibrosis regression properties. Methods Sprague-Dawley (SD) rats (n=18) were separated into three groups (control, untreated liver fibrosis, and UC-MSCs treated group). Serum PDGF-β level was determined by enzymelinked immunosorbent assay (ELISA) following 14 days of UCMSCs injection. Meanwhile, AT1R expression was interpreted based on immunoreactive score (IRS) stained using polyclonal antibody and liver fibrosis stained with hematoxylin & eosin was graded using the METAVIR score. Results UC-MSCs were isolated successfully from rat umbilical cord. Liver fibrosis was observed following 14 weeks of CCl4 injection concurrent with higher serum level of PDGF-β, but the UC-MSCs-treated group had lower level (980.08 ±289.41 and 606.42±109.85 for untreated liver fibrosis and UC-MSCs treated group, respectively; p=0.004). There was also a high expression of AT1R among untreated liver fibrosis group, as well as highgrade liver fibrosis versus localized fibrosis and low level of AT1R expression among UC-MSCs treated-group (p=0.001). Conclusion UC-MSCs administration could ameliorate liver fibrosis by reducing the AT1R expression and PDGF-β serum levels, and intervention through this signaling pathway could be alternative evidence for the causative of positive outcome.

Keywords

• immunohistochemistry
• liver cirrhosis
• mesenchymal stem cell transplantation