RT info:eu-repo/semantics/article
T1 Mesenchymal stromal cells combined with elastin-like recombinamers increase angiogenesis in vivo after hindlimb ischemia
A1 Ibáñez Fonseca, Arturo
A1 Rico, Ana
A1 Preciado, Silvia
A1 González Pérez, Fernando
A1 Muntión, Sandra
A1 García Briñón, Jesús
A1 García Macías, María Carmen
A1 Rodríguez Cabello, José Carlos
A1 Pericacho, Miguel
A1 Alonso Rodrigo, Matilde
A1 Sánchez Guijo, Fermín
K1 Células
K1 Isquemia
K1 Medicina regenerativa
K1 Mesenchymal stromal cells
K1 Células estromales mesenquimales
K1 Biomaterials
K1 Biomateriales
K1 Angiogenesis
K1 2407 Biología Celular
AB Hindlimb ischemia is an unmet medical need, especially for those patients unable to undergo vascular surgery. Cellular therapy, mainly through mesenchymal stromal cell (MSC) administration, may be a potentially attractive approach in this setting. In the current work, we aimed to assess the potential of the combination of MSCs with a proangiogenic elastin-like recombinamer (ELR)–based hydrogel in a hindlimb ischemia murine model. Human bone marrow MSCs were isolated from four healthy donors, while ELR biomaterials were genetically engineered. Hindlimb ischemia was induced through ligation of the right femoral artery, and mice were intramuscularly injected with ELR biomaterial, 0.5 × 106 MSCs or the combination, and also compared to untreated animals. Tissue perfusion was monitored using laser Doppler perfusion imaging. Histological analysis of hindlimbs was performed after hematoxylin and eosin staining. Immunofluorescence with anti–human mitochondria antibody was used for human MSC detection, and the biomaterial was detected by elastin staining. To analyze the capillary density, immunostaining with an anti–CD31 antibody was performed. Our results show that the injection of MSCs significantly improves tissue reperfusion from day 7 (p = 0.0044) to day 21 (p = 0.0216), similar to the infusion of MSC + ELR (p = 0.0038, p = 0.0014), without significant differences between both groups. After histological evaluation, ELR hydrogels induced minimal inflammation in the injection sites, showing biocompatibility. MSCs persisted with the biomaterial after 21 days, both in vitro and in vivo. Finally, we observed a higher blood vessel density when mice were treated with MSCs compared to control (p<0.0001), but this effect was maximized and significantly different to the remaining experimental conditions when mice were treated with the combination of MSCs and the ELR biomaterial (p < 0.0001). In summary, the combination of an ELR-based hydrogel with MSCs may improve the angiogenic effects of both strategies on revascularization of ischemic tissues.
PB Frontiers Media
SN 2296-4185
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/55057
UL https://uvadoc.uva.es/handle/10324/55057
LA eng
NO Frontiers in Bioengineering and Biotechnology, 2022, vol.10, artículo 918602
NO Producción Científica
DS UVaDOC
RD 11-jul-2024