Title |
Synergistic Actions of Hematopoietic and Mesenchymal Stem/Progenitor Cells in Vascularizing Bioengineered Tissues
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Published in |
PLOS ONE, December 2008
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DOI | 10.1371/journal.pone.0003922 |
Pubmed ID | |
Authors |
Eduardo K. Moioli, Paul A. Clark, Mo Chen, James E. Dennis, Helaman P. Erickson, Stanton L. Gerson, Jeremy J. Mao |
Abstract |
Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs) and mesenchymal stem/progenitor cells (MSCs) were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP) scaffolds, followed by infusion of gel-suspended CD34(+) hematopoietic cells. Co-transplantation of CD34(+) HSCs and CD34(-) MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromised mice yielded vascularized tissue. The average vascular number of co-transplanted CD34(+) and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34(+) cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34(+) cells. Based on additional in vitro results of endothelial differentiation of CD34(+) cells by vascular endothelial growth factor (VEGF), we adsorbed VEGF with co-transplanted CD34(+) and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34(+) cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone, adipose, muscle and dermal grafts, and may have implications in the regeneration of internal organs. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 2% |
Switzerland | 1 | <1% |
Germany | 1 | <1% |
Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 111 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 26% |
Researcher | 23 | 20% |
Student > Master | 17 | 15% |
Professor > Associate Professor | 10 | 9% |
Professor | 9 | 8% |
Other | 22 | 19% |
Unknown | 6 | 5% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 33 | 28% |
Agricultural and Biological Sciences | 32 | 27% |
Engineering | 15 | 13% |
Biochemistry, Genetics and Molecular Biology | 9 | 8% |
Materials Science | 6 | 5% |
Other | 10 | 9% |
Unknown | 12 | 10% |