Accession Number:

AD1023952

Title:

Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

Descriptive Note:

Technical Report,30 Sep 2011,29 Sep 2015

Corporate Author:

University of Pittsburgh Pittsburgh United States

Personal Author(s):

Report Date:

2015-12-01

Pagination or Media Count:

11.0

Abstract:

These studies are focused on expanding human hepatocytes from control, marginal quality and cirrhotic livers for the treatment of life-threatening acute liver failure. Two technical objectives were proposed 1. to characterize and expand hepatocytes from patients with cirrhosis and end-stage liver disease in immune deficient hosts whose livers permit extensive repopulation with donor cells, and 2 to determine the extent to which transplantation with human hepatocytes can reverse hepatic failure in a clinically relevant non-human primate model of this process. In order to accomplish these objectives, we have explored the range of liver diseases that allow expansion of human hepatocytes in FRG mice and have isolated the human hepatocytes for use in a non-human primate model of acute liver failure. We have also performed additional studies on hepatocytes isolated from the livers of rats with end-stage cirrhosis, identified a target molecule that control sliver-specific gene expression in these cells and demonstrated that re-expression of this gene, HNF4, , results in normalization of hepatocyte function in vitro and in vivo. We have also induced acute liver failure in monkeys and transplanted these animals with human hepatocytes. We have now successfully corrected liver failure in two animals transplanted with human hepatocytes as we optimized the protocol for inducing acute liver failure. Most importantly. in each case we have demonstrated that we can recover an adequate number of human hepatocytes from repopulated FRG mice for transplantation in a primate model, indicating this approach could be used for patients.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE