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Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets.
- Source :
-
Cell transplantation [Cell Transplant] 2012; Vol. 21 (6), pp. 1305-20. Date of Electronic Publication: 2012 Mar 22. - Publication Year :
- 2012
-
Abstract
- The efficacy of islet transplantation is limited by poor graft vascularization. We herein demonstrated that microvesicles (MVs) released from endothelial progenitor cells (EPCs) enhanced human islet vascularization. After incorporation into islet endothelium and β-cells, EPC-derived MVs favored insulin secretion, survival, and revascularization of islets transplanted in SCID mice. MVs induced in vitro islet endothelial cell proliferation, migration, resistance to apoptosis, and organization in vessel-like structures. Moreover, MVs partially overcame the antiangiogenic effect of rapamycin and inhibited endothelial-leukocyte interaction via L-selectin and CD40. MVs were previously shown to contain defined patterns of mRNAs. Here we demonstrated that MVs carried the proangiogenic miR-126 and miR-296 microRNAs (miRNAs). MVs pretreated with RNase or derived from Dicer knocked-down EPCs showed a reduced angiogenic effect. In addition, MVs overcame the antiangiogenic effect of the specific antagomiRs of miR-126 and miR-296, suggesting a relevant contribution of miRNAs delivered by MVs to islet endothelium. Microarray analysis of MV-stimulated islet endothelium indicated the upregulation of mRNAs coding for factors involved in endothelial proliferation, differentiation, and angiogenesis. In addition, MVs induced the activation of the PI3K-Akt and eNOS signaling pathways in islet endothelium. These results suggest that MVs activate an angiogenic program in islet endothelium that may sustain revascularization and β-cell function.
- Subjects :
- Angiogenesis Inhibitors pharmacology
Animals
Apoptosis
CD40 Antigens metabolism
Cell Proliferation
DEAD-box RNA Helicases antagonists & inhibitors
DEAD-box RNA Helicases genetics
DEAD-box RNA Helicases metabolism
Humans
Insulin metabolism
Insulin Secretion
Insulin-Secreting Cells metabolism
Islets of Langerhans metabolism
Islets of Langerhans Transplantation
L-Selectin metabolism
Leukocytes cytology
Leukocytes immunology
Mice
Mice, SCID
MicroRNAs metabolism
Nitric Oxide Synthase Type III metabolism
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Ribonuclease III antagonists & inhibitors
Ribonuclease III genetics
Ribonuclease III metabolism
Ribonucleases metabolism
Signal Transduction
Sirolimus pharmacology
Transplantation, Heterologous
Endothelial Cells cytology
Islets of Langerhans blood supply
Neovascularization, Physiologic
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1555-3892
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 22455973
- Full Text :
- https://doi.org/10.3727/096368911X627534