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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
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Isolation of CD133+ Liver Stem Cells for Clonal Expansion
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Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure.

Biju Parekkadan1, Daan van Poll, Kazuhiro Suganuma

  • 1Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts, USA.

Plos One
|September 27, 2007
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Mesenchymal stem cell (MSC) molecules, delivered via conditioned medium or bioreactor, significantly improved survival in rats with fulminant hepatic failure (FHF) by altering immune cell migration. This suggests a novel therapeutic approach for inflammatory liver conditions.

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Area of Science:

  • Immunology
  • Hepatology
  • Stem Cell Biology

Background:

  • Modulating the immune system offers an alternative to cellular therapies for fulminant hepatic failure (FHF).
  • Mesenchymal stem cells (MSCs) inhibit immune cells in vitro via paracrine mediators.
  • The in vivo therapeutic potential of MSC-derived molecules in immunological conditions remains largely untested.

Purpose of the Study:

  • To investigate the therapeutic efficacy of MSC-derived molecules in a rat model of FHF.
  • To determine the mechanism by which MSC-derived molecules exert their effects on immune cells and liver pathology.
  • To identify the active components within MSC-derived molecules responsible for therapeutic benefits.

Main Methods:

  • Administration of MSC-derived molecules via intravenous bolus of conditioned medium (MSC-CM) or extracorporeal perfusion with MSCs (MSC-EB) in FHF rats.
  • Histopathological analysis of liver tissues to assess inflammation, cell death, and tissue repair.
  • Computed tomography (CT) imaging to track leukocyte migration patterns.
  • Proteomic analysis (protein array) and biochemical fractionation (heparin binding affinity) of MSC-CM to identify active components.

Main Results:

  • MSC-CM and MSC-EB administration significantly improved survival rates in FHF rats, demonstrating a cell mass-dependent therapeutic window.
  • Histopathology revealed reduced leukocytic infiltrates, hepatocellular death, and bile duct abnormalities in MSC-CM treated livers.
  • CT scans showed that MSC-CM functionally diverts immune cells away from the injured liver.
  • Protein array and fractionation identified chemokines within the heparin-bound fraction of MSC-CM as key active components.

Conclusions:

  • MSC-derived molecules, particularly chemokines, offer a promising therapeutic strategy for FHF by modulating immune cell migration.
  • This study provides the first experimental evidence for the medicinal use of MSC-derived molecules in treating inflammatory conditions like FHF.
  • Altered leukocyte migration mediated by MSC-derived molecules represents a novel therapeutic modality for FHF.