Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.
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 mesenchyma...
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2008
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oai:doaj.org-article:045d30513fd44c89870ae467a2e17a872021-11-25T06:18:11ZSynergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.1932-620310.1371/journal.pone.0003922https://doaj.org/article/045d30513fd44c89870ae467a2e17a872008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19081793/?tool=EBIhttps://doaj.org/toc/1932-6203Poor 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.Eduardo K MoioliPaul A ClarkMo ChenJames E DennisHelaman P EricksonStanton L GersonJeremy J MaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 12, p e3922 (2008) |
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Medicine R Science Q Eduardo K Moioli Paul A Clark Mo Chen James E Dennis Helaman P Erickson Stanton L Gerson Jeremy J Mao Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
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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. |
format |
article |
author |
Eduardo K Moioli Paul A Clark Mo Chen James E Dennis Helaman P Erickson Stanton L Gerson Jeremy J Mao |
author_facet |
Eduardo K Moioli Paul A Clark Mo Chen James E Dennis Helaman P Erickson Stanton L Gerson Jeremy J Mao |
author_sort |
Eduardo K Moioli |
title |
Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
title_short |
Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
title_full |
Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
title_fullStr |
Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
title_full_unstemmed |
Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
title_sort |
synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doaj.org/article/045d30513fd44c89870ae467a2e17a87 |
work_keys_str_mv |
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