Comparison of the therapeutic effects of hUC-MSC intravenous delivery and intraperitoneal administration of MSCs encapsulated in alginate capsules for the treatment of rat liver cirrhosis

Abstract

Mesenchymal stem cells are the most promising regenerative medicine tool for the treatment of various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury, but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in the implementation of MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and normalization of the morphometric parameters of liver parenchyma cells. The expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both methods of transplantation, however, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.

About MSC

“…The dynamics of liver restoration in rats with hepatic cirrhosis, induced by the administration of CCl 4 . Accord ing to Rymar S. et al [23]. Under a single administration of MSC, the process of restoring serious da ma ges in the liver starts and develops for a long time.…”

“…In this model, the therapeutic effect of MSCs appears to be independent of their cel lular activity and depends on a mechanism [23] potentially involving recognition and phago cytosis of MSCs by monocytic cells." [19].…”

“…The dynamics of acute in flammation after MSC induction was studied one hour later.In case of acute damage, the therapeutic effect starts very fast. According of Rymar et al[23]…”

Effects of transplantation of preconditioned mesenchymal stem cells seeded on a biomimetic 3D scaffold

“…hUC-MSC were isolated from umbilical cords of healthy donors (39-40 weeks gestation) by the explant method described earlier [6]. According to the minimal criteria for defining multipotent mesenchymal stromal cells, the CD90, CD73, CD105, CD34 and CD45 surface markers expression was verified on the second passage by FACS analysis ( BD FACS Aria, USA), using the FITC Mouse Anti-Human CD90 (#561969), APC Mouse anti-Human CD73 (#560847), PerCP-Cy™5.5 Mouse anti-Human CD105 (#560819), FITC Mouse Anti-Human CD45(#555482), APC Mouse Anti-Human CD34 (#555824) as described in [7]. The ability of the cells to undergo osteogenic, adipogenic, and chondrogenic differentiation was assessed previously [7].…”