Adipose-derived stromal vascular fraction cells isolated from old animals exhibit reduced capacity to support the formation of microvascular networks.

UNLABELLED: Adipose-derived regenerative and stem cells, defined collectively as the stromal vascular fraction (SVF), support the formation of neovascular networks at the site of implantation. The effect of advancing age on SVF cell population effectiveness towards stimulated neovascularization was evaluated. METHODS: SVF was enzymatically isolated from adipose of young (ySVF, 4 months) or old (oSVF, 24 months) Fisher-344 rats, combined with type I collagen and polymerized. Encapsulated SVF was implanted subcutaneously into young Rag1 mice for two or four weeks. Angiogenic function of age-dependent SVF was also extensively evaluated in vitro using standard assays. RESULTS: In vitro studies indicated no difference in angiogenic function between ySVF and oSVF (viability, proliferation, migration, and tube-formation). At two weeks post-implantation, there was no age-related difference in percent apoptosis in explanted constructs. By four weeks post-implantation, oSVF implants displayed 36% less total vessels/mm(2), 43% less perfused vessels/mm(2), and exhibited greater percent apoptosis compared to ySVF (n ≥ 12). Blocking thrombospondin-1 (Thbs-1), a protein found to be highly expressed in oSVF but not ySVF, increased the percent of perfused vascular volume and vessel diameters in oSVF constructs after two weeks compared to oSVF implants treated with control antibody. CONCLUSIONS: Advancing donor age reduces the potential of adipose-derived SVF to derive a mature microcirculation, but does not hinder initial angiogenesis. However, modulation of Thbs-1 may improve this outcome. This data suggests that greater pruning, dysfunctional structural adaptation and/or poor maturation with initiation of blood flow may occur in oSVF.

Targeting the Vessel Underdogs: Therapeutic Approaches for Microvessel Dysfunction in the Heart.

From an obscure and overlooked beginning, the function of the microvessels in the heart has received increasing attention after the Women's Ischemia Syndrome Evaluation study concluded roughly a decade ago. This review defines the contribution of the coronary microcirculation in the development of heart disease and focuses on the therapeutic methods to reverse coronary microvascular dysfunction. Tissue engineering approaches in the past have largely neglected vascular cells in the attempts to design augmented myocardial tissue, but groups are now making advances that incorporate a functional microcirculation with cardiomyocytes that may advance this line of research. This review covers the definition and classification of coronary microvascular disease, as well as the successful (and unsuccessful) therapeutic approaches in the literature.