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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
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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...
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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells
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Mesenchymal stem cells support hepatocyte function in engineered liver grafts.

Yoshie Kadota1, Hiroshi Yagi1, Kenta Inomata1

  • 1Department of Surgery; Keio University; School of Medicine; Tokyo, Japan.

Organogenesis
|February 4, 2014
PubMed
Summary

Mesenchymal stem cells (MSCs) enhance engineered liver function when co-cultured with hepatocytes in decellularized scaffolds. This regenerative therapy approach shows promise for future clinical applications in liver regeneration.

Keywords:
cell transplantationorgan transplantationregenerative medicinescaffold matrixstem celltissue engineering

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Area of Science:

  • Regenerative Medicine
  • Tissue Engineering
  • Hepatology

Background:

  • Organ decellularization offers a promising platform for regenerative therapy, utilizing native matrices for cell integration.
  • Identifying optimal cell sources for artificial livers, including primary hepatocytes and supportive cells like mesenchymal stem cells (MSCs), is crucial.

Purpose of the Study:

  • To investigate the potential of co-culturing bone marrow-derived MSCs with primary hepatocytes in engineered liver scaffolds.
  • To evaluate the enhancement of hepatic function and graft vascularization following transplantation of these co-recellularized scaffolds.

Main Methods:

  • Decellularization of whole-liver scaffolds.
  • Sequential infusion and co-cultivation of primary hepatocytes and bone marrow-derived MSCs.
  • Transplantation of co-recellularized liver scaffolds into live animal models.
  • Assessment of graft vascularization and expression of key molecules post-transplantation.

Main Results:

  • Co-cultivation of MSCs with hepatocytes in engineered liver scaffolds enhanced hepatic function.
  • Transplanted co-recellularized scaffolds demonstrated upregulated expression of adhesion molecules and proangiogenic factors after blood flow establishment.
  • MSCs demonstrated potential to modulate hepatic regeneration and enhance cell preservation.

Conclusions:

  • Co-recellularization of decellularized liver scaffolds with MSCs and hepatocytes represents a viable strategy for enhancing engineered liver function.
  • This approach shows potential for improving graft vascularization and therapeutic efficacy in regenerative liver therapy.