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Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells

Biju Parekkadan1, Daan van Poll, Zaki Megeed

  • 1Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, 51 Blossom Street, Boston, MA 02114, USA.

Biochemical and Biophysical Research Communications
|September 18, 2007
PubMed

Insights

Mesenchymal stem cells (MSCs) inhibit liver fibrosis by modulating hepatic stellate cells (SCs) through paracrine signaling. MSCs reduce SC proliferation and collagen production while inducing SC apoptosis, clarifying their therapeutic mechanism.

Area of Science:

  • Stem cell biology
  • Hepatology
  • Immunology

Background:

  • Mesenchymal stem cells (MSCs) show promise in preclinical liver fibrosis models.
  • The precise therapeutic mechanisms of MSCs in liver fibrosis remain unclear.

Purpose of the Study:

  • To investigate if MSCs modulate hepatic stellate cell (SC) activity via paracrine mechanisms.
  • To elucidate the molecular pathways involved in MSC-mediated SC modulation.

Main Methods:

  • Indirect co-culture of MSCs and activated SCs.
  • Analysis of collagen deposition, SC proliferation, and apoptosis.
  • Investigation of cytokine secretion (IL-6, IL-10, TNF-alpha) and growth factor (HGF) involvement.
  • Antibody-neutralization studies to block specific molecular interactions.

Main Results:

  • Indirect co-culture significantly decreased collagen deposition and SC proliferation while increasing SC apoptosis.
  • MSCs secreted IL-10 in response to SC-derived IL-6.
  • Blocking MSC-derived IL-10 and TNF-alpha abolished the inhibitory effects on SC proliferation and collagen synthesis.
  • MSC-derived HGF was responsible for inducing SC apoptosis.

Conclusions:

  • MSCs modulate activated SC function through paracrine mechanisms, including IL-10, TNF-alpha, and HGF.
  • These findings provide a mechanistic explanation for the protective role of MSCs in liver fibrosis.
  • The identified mechanisms may be relevant to other fibrotic conditions.

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