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| Home > Articles > Published articles > Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium : |
(Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau)| Date: | 2017 |
| Abstract: | Myocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI. Pig subcutaneous adipose tissue ASCs were isolated, expanded and GFP-labeled. ASC angiogenic function was assessed by the in-vivo chick chorioallantoic membrane (CAM) model. Pigs underwent MI induction and 7 days after were randomized to receive: allogenic ASCs (intracoronary infusion); conditioned media (CM; intravenous infusion); ASCs + CM; or PBS/placebo (control). Cardiac damage and function were monitored by 3-T cardiac magnetic resonance imaging upon infusion (baseline CMR) and 1 and 3 weeks thereafter. We assessed in the myocardium: microvessel density; angiogenic markers (CD105, CD31, TF, VEGFR2, VEGFR1, vWF, eNOS, CD62); collagen deposition; and reparative fibrosis (TGFβ/TβRII/collagen). Differential proteomics of ASCs and CM was performed to characterize the ASC protein signature. CAM indicated a significant ASC proangiogenic capacity. In pigs after MI, only PBS/placebo animals displayed an impaired cardiac function 3 weeks after infusion (p < 0. 05 vs baseline). Administration of ASCs + CM significantly enhanced neovessel formation and favored cardiac repair post MI (p < 0. 05 vs the other groups). Molecular markers of angiogenesis were significantly upregulated both at transcriptional and protein levels (p < 0. 05). The in-silico bioinformatics analysis of the ASC and CM proteome (interactome) indicated activation of a coordinated protein network involved in the formation of microvessels and the resolution of rarefaction. Coadministration of allogenic ASCs and their CM synergistically contribute to the neovascularization of the infarcted myocardium through a coordinated upregulation of the proangiogenic protein interactome. The online version of this article (doi:10. 1186/s13287-017-0509-2) contains supplementary material, which is available to authorized users. |
| Grants: | Instituto de Salud Carlos III CB16-11-00411 Ministerio de Ciencia e Innovación PNS-SAF2016-76819-R Ministerio de Ciencia e Innovación PNS-2015-71653-R Instituto de Salud Carlos III CPII13-00012 |
| Note: | Altres ajuts: This work was supported by the Spanish Cardiovascular Network of Cell Therapy (Red TerCel RD16/0011/018) and Ciber CV(CB16/11/00411) from the Instituto Salud Carlos III (to LB). Additional funding was received from Plan Nacional de Salud (PNS SAF2016-76819-R to LB, 2015-71653-R to GV) from the Spanish Ministry of Science and Innovation and FEDER funds; from Instituto de Salud Carlos III (CPII13/00012 to GA); and support from a grant from the Muy Ilustrísima Administración from the Hospital de la Santa Creu I Sant Pau (to MG). The authors thank Fundacion Jesus Serra, Barcelona for continuous support. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Allogenic adipose-derived stem cells ; Conditioned media ; Angiogenesis ; Myocardial infarction ; Proteomics ; Systems biology |
| Published in: | Stem cell research & therapy, Vol. 8 (march 2017) , ISSN 1757-6512 |
