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Cardiovasc Res. 2015 Oct 1;108(1):39-49. doi: 10.1093/cvr/cvv197. Epub 2015 Jul 17.

Transplantation of adipose tissue mesenchymal cells conjugated with VEGF-releasing microcarriers promotes repair in murine myocardial infarction.

Author information

1
Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy.
2
Biocenter Kuopio, A. I. Virtanen Institute for Molecular Sciences, Kuopio, Finland.
3
Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, 'G. d'Annunzio' University, Chieti, Italy.
4
Department of Medicine and Aging Sciences, 'G. d'Annunzio' University, Chieti, Italy.
5
INSERM U 1066, Micro et nanomédecine biomimétiques, LUNAM, Université d'Angers, Angers, France.
6
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
7
Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, 'G. d'Annunzio' University, Chieti, Italy rdecater@unich.it.

Abstract

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 µL, n = 7), AMI followed by intramyocardial injection with AT-MSCs (2.5 × 10(5) cells/20 µL, n = 5), or concentrated medium (CM) from AT-MSCs (20 µL, n = 8), or AT-MSCs (2.5 × 10(5) cells/20 µL) 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.

KEYWORDS:

Adipose tissue-derived mesenchymal stromal cells; Microspheres; Myocardial infarction

PMID:
26187727
DOI:
10.1093/cvr/cvv197
[Indexed for MEDLINE]

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