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Terminal differentiation is not a major determinant for the success of stem cell therapy - Cross-talk between muscle-derived stem cells and host cells

Gharaibeh, B and Lavasani, M and Cummins, JH and Huard, J (2011) Terminal differentiation is not a major determinant for the success of stem cell therapy - Cross-talk between muscle-derived stem cells and host cells. Stem Cell Research and Therapy, 2 (4).

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We have found that when muscle-derived stem cells (MDSCs) are implanted into a variety of tissues only a small fraction of the donor cells can be found within the regenerated tissues and the vast majority of cells are host derived. This observation has also been documented by other investigators using a variety of different stem cell types. It is speculated that the transplanted stem cells release factors that modulate repair indirectly by mobilizing the host's cells and attracting them to the injury site in a paracrine manner. This process is loosely called a 'paracrine mechanism', but its effects are not necessarily restricted to the injury site. In support of this speculation, it has been reported that increasing angiogenesis leads to an improvement of cardiac function, while inhibiting angiogenesis reduces the regeneration capacity of the stem cells in the injured vascularized tissues. This observation supports the finding that most of the cells that contribute to the repair process are indeed chemo-attracted to the injury site, potentially through host neo-angiogenesis. Since it has recently been observed that cells residing within the walls of blood vessels (endothelial cells and pericytes) appear to represent an origin for post-natal stem cells, it is tempting to hypothesize that the promotion of tissue repair, via neo-angiogenesis, involves these blood vessel-derived stem cells. For non-vascularized tissues, such as articular cartilage, the regenerative property of the injected stem cells still promotes a paracrine, or bystander, effect, which involves the resident cells found within the injured microenvironment, albeit not through the promotion of angiogenesis. In this paper, we review the current knowledge of post-natal stem cell therapy and demonstrate the influence that implanted stem cells have on the tissue regeneration and repair process. We argue that the terminal differentiation capacity of implanted stem cells is not the major determinant of the cells regenerative potential and that the paracrine effect imparted by the transplanted cells plays a greater role in the regeneration process. © 2011 BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Lavasani, M
Cummins, JH
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 12 September 2011
Date Type: Publication
Journal or Publication Title: Stem Cell Research and Therapy
Volume: 2
Number: 4
DOI or Unique Handle: 10.1186/scrt72
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
Swanson School of Engineering > Bioengineering
Refereed: Yes
Article Type: Review
MeSH Headings: Animals; Cartilage Diseases--pathology; Cartilage Diseases--therapy; Cell Differentiation; Cell- and Tissue-Based Therapy; Cellular Microenvironment; Heart Diseases--pathology; Heart Diseases--therapy; Humans; Mice; Muscle Fibers, Skeletal--cytology; Muscle Fibers, Skeletal--physiology; Neovascularization, Pathologic; Paracrine Communication; Regeneration; Stem Cell Transplantation; Stem Cells--cytology; Stem Cells--physiology
Other ID: NLM PMC3219062
PubMed Central ID: PMC3219062
PubMed ID: 21745421
Date Deposited: 04 Apr 2014 16:38
Last Modified: 02 Feb 2019 14:56


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