Transdifferentiation of bioencapsulated bone marrow cells into hepatocyte-like cells in the 90% hepatectomized rat model

Abstract

Under specific conditions, bone marrow cells can transdifferentiate into a variety of cell types including hepatocytes. In this study, bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized rats. We then followed the transdifferentiation of the bone marrow cells and the effect of this on liver regeneration in this liver failure model. Bone marrow cells isolated from Wistar rats were bioencapsulated using alginate-polylysine-alginate method. These bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized Wistar rats. Blood chemistry, HGF, liver weight, and survival of the recipient rats were evaluated. Histology and immunocytochemistry were used to analyze the bioencapsulated cells before and 14 days after transplantation. Unlike free bone marrow cells, transplantation of bioencapsulated bone marrow cells improved the survival of 90% hepatectomized rats and improved the blood chemistry with an efficacy similar to that of bioencapsulated hepatocytes or free hepatocytes transplantation. Some bioencapsulated bone marrow cells expressed hepatocytes markers of cytokeratins 8, cytokeratins 18, albumin, and AFP after 2 weeks of transplantation. These results suggest that syngeneic bioencapsulated bone marrow cells can transdifferentiate into hepatocyte-like cells in the peritoneal cavity of 90% hepatectomized rats and increased the survival rates of these rats. In conclusion, these findings suggest the potential for a new alternative to hepatoctye transplantation for cellular therapy of acute liver failure. Liver Transpl 12: 566-572, 2006.

Bone Marrow-Derived Mononuclear Cells Differentiate into Hepatocyte-Like Cells within Few Hrs without Fusion

“…Our results favor the differentiation hypothesis, in accordance with other study that used microencapsulated cells [15]. Liu and Chang [15] have shown that BMMC encapsulated with the APA (Alginate-PolylysineAlginate) method improve survival in a 90% partial hepatectomy rat model of acute liver failure. In addition, they found that some BMMC express ALB, AFP, CK 8, CK 18 and were able to store glycogen, after 2 weeks of transplantation.…”

“…Most of these studies show the expression of Alb and Afp [12][13][14][15]17,33], but also Ck8 and Ck18 [15]. As in the previous studies, this differentiation occurs only when BMMC are transplanted into injured animals, suggesting that liver damage triggers the release of substances that modulate BMMC gene expression.…”

“…It has been demonstrated that the alginate microenvironment maintains cell viability, is conducive to embryonic stem cell differentiation into hepatocytes, and maintains differentiated cellular function [26]. In addition, encapsulated bone marrow cells showed evidence of glycogen synthesis and expression of typical markers of hepatocytes, after transplantation in the 90% liver failure model [15,27].…”

New Horizons in Pediatric Hepatology: A Glimpse of the Future

“…Soluble factors such as growth factors, cytokines, extracellular matrix glycoproteins and other small molcules produced by MSCs likely mediate these effects in ALF rather than transdifferentiation [58]. Candidate molecules include interleukin (IL)-1Rα, IL6, IL8, granulocyte-colony-stimulating factor, nerve growth factor and hepatocyte growth factor [60,62]. MSC-conditioned medium conferred a significant improvement in mortality and biochemical indices of liver damage in a galactosamine-injured rat with evidence of inhibition of apoptosis and promotion of liver regeneration in the treated liver [63].…”

First Design and Clinical Use in Patients of Surface Modified Sorbent Hemoperfusion Based on Artificial Cells for Poisoning, Kidney Failure, Liver Failure and Immunology

“…One line of research is to combine this with the use of hepatocytes perfusion system (Rozga et al, 1993;Sussman et al, 1994). Another approach is to combine this with artificial cells containing hepatocytes or stem cells (Chang, 2007a(Chang, , 2007b(Chang, , 2007c(Chang, , 2007d(Chang, , 2010(Chang, , 2014Liu and Chang, 2005, 2006a, 2006b, 2009, 2012.…”