In vitro pro-angiogenic effects of human adipose derived multipotent mesenchymal stromal cells: effect of donor's age

• Published in: Cytotherapy (Oxford, England) England), 2020-05, Vol.22 (5), p.S76-S77
• Main Authors: Jeon, P., Lora, M., Hussain, S., Farge, D., Hudson, M., Colmegna, I.
• Format: Article
• Language: English
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2020.03.122

Multipotent mesenchymal stromal cells (MSCs) play a pivotal role in regulating blood vessel formation and promoting vascular homeostasis. These effects are primarily mediated through trophic factors secreted by MSCs (MSC secretome). Those include angiogenic, anti-apoptotic, and immunomodulatory factors that are essential for vascular network remodeling. We have previously shown that adipose derived MSCs from elderly subjects have impaired immunomodulatory properties compared to those from young donors. A higher content of proinflammatory factors (e.g., IL-6, IL-8/CXCL8, and MCP-1/CCL2) in the secretome of elderly-MSCs mediates their reduced immunopotency. It is unclear if age-related changes in the MSC secretome impact the pro-angiogenic effects of MSCs. Methods: Human adipose derived MSC at passage 4-5 (P4-P5) from six adult (mean age: 66.5±11.6 years) and six pediatric (mean age: 16.5±3.2) healthy donors were evaluated. The effect of MSCs or MSC conditioned media (MSC-CM) on human umbilical vein endothelial cells (HUVEC, P4-P5) was assessed in: (i) migration assays (i.e. trans-well migration of HUVEC towards MSC-CM) and (ii) tube formation assays (i.e. in vitro Matrigel tube formation assay with MSC-CM and MSC:HUVEC co-cultures). ImageJ and Wimasis image systems were used for analysis. Angiogenic factors (i.e., Angiopoietin-2, EGF, Endoglin, FGF-1, Follistatin, HGF, IL-8, PIGF, VEGF-A, VEGF-C) in the MSC-CM were quantified by multiplex arrays. In contrast to pediatric MSC-CM, adult MSC-CM are more effective in inducing HUVEC migration (adult vs pediatric MSC-CM percent increase compared to negative control; mean±SD: 199.1±54.2 vs 80.81±27.6, p