期刊
CARDIOVASCULAR RESEARCH
卷 108, 期 1, 页码 39-49出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvv197
关键词
Adipose tissue-derived mesenchymal stromal cells; Microspheres; Myocardial infarction
资金
- Italian Istituto Nazionale Ricerche Cardiovascolari (I.N.R.C.)
- Italian Ministry of the University and Research (PRIN projects)
- CARIPLO Foundation 'Angers Loire Metropole'
- 'Institut National de le Recherche et de la Sante Medical (INSERM)', France
Rationale Engraftment and survival of transplanted stem or stromal cells in the microenvironment of host tissues may be improved by combining such cells with scaffolds to delay apoptosis and enhance regenerative properties. Aims We examined whether poly(lactic-co-glycolic acid) pharmacologically active microcarriers (PAMs) releasing vascular endothelial growth factor (VEGF) enhance survival, differentiation, and angiogenesis of adipose tissue-mesenchymal stromal cells (AT-MSCs). We analysed the efficacy of transplanted AT-MSCs conjugated with PAMs in a murine model of acute myocardial infarction (AMI). Methods and results We used fibronectin-coated (empty) PAMs or VEGF-releasing PAMs covered with murine AT-MSCs. Twelve-month-old C57 mice underwent coronary artery ligation to induce AMI, and were randomized into five treatment groups: AMI control (saline 20 mu L, n = 7), AMI followed by intramyocardial injection with AT-MSCs (2.5 x 10(5) cells/20 mu L, n = 5), or concentrated medium (CM) from AT-MSCs (20 mu L, n = 8), or AT-MSCs (2.5 x 10(5) cells/20 mu L) conjugated with empty PAMs (n = 7), or VEGF-releasing PAMs (n = 8). Sham-operated mice (n = 7) were used as controls. VEGF-releasing PAMs increased proliferation and angiogenic potential of AT-MSCs, but did not impact their osteogenic or adipogenic differentiation. AT-MSCs conjugated with VEGF-releasing PAMs inhibited apoptosis, decreased fibrosis, increased arteriogenesis and the number of cardiac-resident Ki-67 positive cells, and improved myocardial fractional shortening compared with AT-MSCs alone when transplanted into the infarcted hearts of C57 mice. With the exception of fractional shortening, all such effects of AT-MSCs conjugated with VEGF-PAMs were paralleled by the injection of CM. Conclusions AT-MSCs conjugated with VEGF-releasing PAMs exert paracrine effects that may have therapeutic applications.
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