Mesenchymal Stromal Cells Combined With Elastin-Like Recombinamers Increase Angiogenesis In Vivo After Hindlimb Ischemia

Frontiers in Bioengineering and Biotechnology

Arturo Ibáñez-Fonseca¹  Fernando González-Pérez¹  Ana Rico²  José Carlos Rodríguez-Cabello³  Matilde Alonso³  Jesús García-Briñón⁴  Sandra Muntión⁵  María-Carmen García-Macías⁵  Fermín Sánchez-Guijo⁵  Silvia Preciado⁵  Miguel Pericacho⁸ 

[1] BIOFORGE Lab, University of Valladolid, CIBER-BBN, Valladolid, Spain;Cell Therapy Unit, Hematology Department, University Hospital of Salamanca, Salamanca, Spain;Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain;Departamento de Biología Celular y Patología, Facultad de Medicina, Salamanca, Spain;Department of Medicine and Cancer Research Center, University of Salamanca, Salamanca, Spain;Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain;RICORS TERAV, ISCIII, Madrid, Spain;Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain;

关键词: mesenchymal stromal cells;    biomaterials;    elastin-like recombinamers;    hindlimb ischemia;    angiogenesis;    mesenchymal stem cells;   

DOI  :  10.3389/fbioe.2022.918602

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown