Juxtacrine and paracrine interactions of rat marrow-derived mesenchymal stem cells, muscle-derived satellite cells, and neonatal cardiomyocytes with endothelial cells in angiogenesis dynamics.
Research into angiogenesis has contributed to progress in the fast-moving field of regenerative medicine. Designing coculture systems is deemed a helpful method to understand the dynamic interaction of various cells involved in the angiogenesis process. We investigated the juxtacrine and paracrine interaction between 3 different cells, namely rat marrow-derived mesenchymal stem cells (rMSCs), rat muscle-derived satellite cells (rSCs), and rat neonatal cardiomyocytes (rCMs), and endothelial cells (ECs) during angiogenesis process. In vitro Matrigel angiogenesis assay was performed whereby ECs were monocultured or cocultured with rMSCs, rSCs, and rCMs or their conditioned media (CM). In addition, in vivo Matrigel plug assay for angiogenesis was conducted to assess the angiogenic potential of the rCM-, rMSC-, and rSC-derived CM. Our results demonstrated that the rMSCs, rSCs, and rCMs elongated along the EC tubules, whereas the rMSCs formed tube-like structures with sprouting tip cells, leading to improved angiogenesis in the coculture system. Moreover, the rMSC- and rSC-derived CM significantly improved angiogenesis tube formation on Matrigel, accelerated EC chemotaxis, and increased the arteriolar density, vascularization index, and vascularization flow index in the Matrigel plug in vivo. Western blotting showed that rMSCs secreted a high level of vascular endothelial growth factor, basic fibroblast growth factor, and stromal-derived factor-1-alpha. Tie2 is also shed from rMSCs. This study demonstrated that stem cells interact with ECs in the juxtacrine and paracrine manner during angiogenesis, and marrow MSCs have superior angiogenic properties.
Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Reza
R
Rahbarghazi
Seyed Mahdi
SM
Nassiri
Parvaneh
P
Khazraiinia
Abdol-Mohammad
AM
Kajbafzadeh
Seyed Hossein
SH
Ahmadi
Elham
E
Mohammadi
Mohammad
M
Molazem
Mohamad
M
Zamani-Ahmadmahmudi
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002633:Chemotaxis; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D042783:Endothelial Cells / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D011509:Proteoglycans / Q000737:chemistry; D051381:Rats; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen