AIMS: In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model. METHODS AND RESULTS: Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups. CONCLUSION: We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.
AIMS: In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model. METHODS AND RESULTS: Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mousemyocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups. CONCLUSION: We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.
Authors: Merry L Lindsey; Yonggang Ma; Elizabeth R Flynn; Michael D Winniford; Michael E Hall; Kristine Y DeLeon-Pennell Journal: Biochim Biophys Acta Mol Basis Dis Date: 2018-09-20 Impact factor: 5.187
Authors: B A Naaijkens; A van Dijk; O Kamp; P A J Krijnen; H W M Niessen; L J M Juffermans Journal: Stem Cell Rev Rep Date: 2014-06 Impact factor: 5.739
Authors: Kristine Y DeLeon-Pennell; Rugmani Padmanabhan Iyer; Yonggang Ma; Andriy Yabluchanskiy; Rogelio Zamilpa; Ying Ann Chiao; Presley L Cannon; Abdullah Kaplan; Courtney A Cates; Elizabeth R Flynn; Ganesh V Halade; Lisandra E de Castro Brás; Merry L Lindsey Journal: Am J Physiol Heart Circ Physiol Date: 2018-05-18 Impact factor: 4.733