Application Prospect of Stem Cell-derived Microvesicles in Regeneration of Injured Tissues_Journal of Biomedical Engineering

Authors：

YINHuiqun ,  JIANGHong

Reproductive Medicine Center, The No. 105 Hospital of PLA, Hefei 230031, China;

Corresponding author：

JIANGHong, Email: jiangh105@sina.com

Keywords：

microvesicle; stem cell; regenerative medicine; tissue regeneration

DOI：

10.7507/1001-5515.20150125

Video：

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More and more evidence indicates that microvesicles (MVs) play a key role in cell-to-cell communication. The MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the cell surface membranes of most types. Components of donor cells are incorporated into MVs that contain bioactive lipids, proteins, genetic cargoes. MVs derived from stem cells may reprogram cells that survived in injury tissue and favor tissue regeneration by delivering their bioactive cargoes to influence the behaviors of recipient cells. Compared with mesenchymal stem cells (MSCs), MVs derived from MSCs were found to mimic the beneficial effects of these cells. These proregenerative effects mediated by MVs can be explained by the fact that MVs are enriched in bioactive lipids, anti-apoptotic and pro-stimulatory growth factors or cytokines, and deliver mRNAs, regulatory miRNAs and proteins that improve overall cell function. Therefore, it opens novel perspectives in exploiting these MVs in tissue regeneration and repair. In addition, the use of MVs instead of stem cells could represent a safe and potentially more advantageous alternative to cell-therapy approaches.

Citation： YINHuiqun, JIANGHong. Application Prospect of Stem Cell-derived Microvesicles in Regeneration of Injured Tissues. Journal of Biomedical Engineering, 2015, 32(3): 688-692. doi: 10.7507/1001-5515.20150125 Copy

1.	FLEISSNER F, GOERZIG Y, HAVERICH A, et al. Microvesicles as novel biomarkers and therapeutic targets in transplantation medicine[J]. Am J Transplant, 2012, 12(2):289-297.
2.	BREAKEFIELD X O, FREDERICKSON R M, SIMPSON R J. Gesicles:microvesicle "cookies" for transient information transfer between cells[J]. Mol Ther, 2011, 19(9):1574-1576.
3.	LEE Y, EL ANDALOUSSI S, WOOD M J. Exosomes and microvesicles:extracellular vesicles for genetic information transfer and gene therapy[J]. Hum Mol Genet, 2012, 21(R1):R125-R134.
4.	GYÖRGY B, SZABÓ T G, PÁSZTÓI M, et al. Membrane vesicles, current state-of-the-art:emerging role of extracellular vesicles[J]. Cell Mol Life Sci, 2011, 68(16):2667-2688.
5.	RATAJCZAK M Z, KUCIA M, JADCZYK T, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine:can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?[J].Leukemia, 2012, 26(6):1166-1173.
6.	OTSURU S, GORDON P L, SHIMONO K, et al. Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms[J]. Blood, 2012, 120(9):1933-1941.
7.	LIANG X, DING Y, ZHANG Y, et al. Paracrine mechanisms of Mesenchymal Stem cell-based therapy:current status and perspectives[J]. Cell Transplant, 2014, 23(9):1045-1509.
8.	JIANG H, QU L, DOU R, et al. Potential role of mesenchymal stem cells in alleviating intestinal ischemia/reperfusion impairment[J]. PLoS One, 2013, 8(9):e74468.
9.	ZHU Y G, FENG X M, ABBOTT J, et al. Human mesenchymal stem cell microvesicles for treatment of E.coli endotoxin-induced acute lung injury in mice[J]. Stem Cells, 2014, 32(1):116-125.
10.	DORRONSORO A, ROBBINS P D. Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes[J]. Stem Cell Res Ther, 2013, 4(2):39-42.
11.	GATTI S, BRUNO S, DEREGIBUS M C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischemiareperfusion-induced acute and chronic kidney injury[J]. Nephrol Dialysis Transplant, 2011, 26(5):1474-1483.
12.	TIMMERS L, LIM S K, ARSLAN F, et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J]. Stem Cell Res, 2007, 1(2):129-137.
13.	CHEN T S, ARSLAN F, YIN Y, et al. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs[J]. J Transl Med, 2011, 9(1):47-57.
14.	CHEN T S, LAI R C, LEE M M, et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs[J]. Nucleic Acids Res, 2010, 38(1):215-224.
15.	YU B, GONG M, WANG Y, et al. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles[J]. PLoS One, 2013, 8(8):e73304.
16.	BRUNO S, GRANGE C, DEREGIBUS M C, et al. Mesenchymal stem cell derived microvesicles protect against acute tubular injury[J]. J Am Soc Nephrol, 2009, 20(5):1053-1067.
17.	COLLINO F, DEREGIBUS M C, BRUNO S, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs[J]. PLoS One, 2010, 5(7):e11803.
18.	BRUNO S, GRANGE C, COLLINO F, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury[J]. PLoS One, 2012, 7(3):e33115.
19.	HE J, WANG Y, SUN S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model[J]. Nephrology (Carlton), 2012, 17(5):493-500.
20.	HERRERA M B, FONSATO V, GATTI S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats[J]. J Cell Mol Med, 2010, 14(6B):1605-1618.
21.	RANGHINO A, CANTALUPPI V, GRANGE C, et al. Endothelial progenitor cell-derived microvesicles improve neovascularization in murine model of hindlimbischemia[J]. Int J Immunopathol Pharmacol, 2012, 25(1):75-85.
22.	CANTALUPPI V, GATTI S, MEDICA D, et al. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells[J]. Kidney Int, 2012, 82(4):412-427.
23.	CANTALUPPI V, BIANCONE L, FIGLIOLINI F, et al. Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets[J]. Cell Transplant, 2012, 21(6):1305-1320.
24.	SALLUSTIO F, COSTANTINO V, COX S N, et al. Human renal stem/progenitor cells repair tubular epithelial cell injury through TLR2-driven inhibin-A and microvesicle-shuttled decorin[J]. Kidney Int, 2013, 83(3):392-403.
25.	WINYARD PJ, PRICE KL. Experimental renal progenitor cells:Repairing and recreating kidneys?[J]. Pediatr Nephrol, 2014, 29(4):665-672.
26.	KATSMAN D, STACKPOLE E J, DOMIN D R, et al. Embryonic stem cell-derived microvesicles induce gene expression changes in Müller cells of the retina[J]. PLoS One, 2012, 7(11):e50417.
27.	RADER D J, PARMACEK M S. Secreted miRNAs suppress atherogenesis[J]. Nat Cell Biol, 2012, 14(3):233-235.
28.	KIM H S, CHOI D Y, YUN S J, et al. Proteomic analysis of microvesicles derived from human mesenchymal stem cells[J]. J Proteome Res, 2012, 11(2):839-849.
29.	ANTHONY D F, SHIELS P G. Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs[J]. Transplant Res, 2013, 2(1):10-18.
30.	ALVAREZ-ERVITI L, SEOW Y, YIN H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]. Nat Biotechnol, 2011, 29(4):341-345.

1. FLEISSNER F, GOERZIG Y, HAVERICH A, et al. Microvesicles as novel biomarkers and therapeutic targets in transplantation medicine[J]. Am J Transplant, 2012, 12(2):289-297.
2. BREAKEFIELD X O, FREDERICKSON R M, SIMPSON R J. Gesicles:microvesicle "cookies" for transient information transfer between cells[J]. Mol Ther, 2011, 19(9):1574-1576.
3. LEE Y, EL ANDALOUSSI S, WOOD M J. Exosomes and microvesicles:extracellular vesicles for genetic information transfer and gene therapy[J]. Hum Mol Genet, 2012, 21(R1):R125-R134.
4. GYÖRGY B, SZABÓ T G, PÁSZTÓI M, et al. Membrane vesicles, current state-of-the-art:emerging role of extracellular vesicles[J]. Cell Mol Life Sci, 2011, 68(16):2667-2688.
5. RATAJCZAK M Z, KUCIA M, JADCZYK T, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine:can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?[J].Leukemia, 2012, 26(6):1166-1173.
6. OTSURU S, GORDON P L, SHIMONO K, et al. Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms[J]. Blood, 2012, 120(9):1933-1941.
7. LIANG X, DING Y, ZHANG Y, et al. Paracrine mechanisms of Mesenchymal Stem cell-based therapy:current status and perspectives[J]. Cell Transplant, 2014, 23(9):1045-1509.
8. JIANG H, QU L, DOU R, et al. Potential role of mesenchymal stem cells in alleviating intestinal ischemia/reperfusion impairment[J]. PLoS One, 2013, 8(9):e74468.
9. ZHU Y G, FENG X M, ABBOTT J, et al. Human mesenchymal stem cell microvesicles for treatment of E.coli endotoxin-induced acute lung injury in mice[J]. Stem Cells, 2014, 32(1):116-125.
10. DORRONSORO A, ROBBINS P D. Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes[J]. Stem Cell Res Ther, 2013, 4(2):39-42.
11. GATTI S, BRUNO S, DEREGIBUS M C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischemiareperfusion-induced acute and chronic kidney injury[J]. Nephrol Dialysis Transplant, 2011, 26(5):1474-1483.
12. TIMMERS L, LIM S K, ARSLAN F, et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J]. Stem Cell Res, 2007, 1(2):129-137.
13. CHEN T S, ARSLAN F, YIN Y, et al. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs[J]. J Transl Med, 2011, 9(1):47-57.
14. CHEN T S, LAI R C, LEE M M, et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs[J]. Nucleic Acids Res, 2010, 38(1):215-224.
15. YU B, GONG M, WANG Y, et al. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles[J]. PLoS One, 2013, 8(8):e73304.
16. BRUNO S, GRANGE C, DEREGIBUS M C, et al. Mesenchymal stem cell derived microvesicles protect against acute tubular injury[J]. J Am Soc Nephrol, 2009, 20(5):1053-1067.
17. COLLINO F, DEREGIBUS M C, BRUNO S, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs[J]. PLoS One, 2010, 5(7):e11803.
18. BRUNO S, GRANGE C, COLLINO F, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury[J]. PLoS One, 2012, 7(3):e33115.
19. HE J, WANG Y, SUN S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model[J]. Nephrology (Carlton), 2012, 17(5):493-500.
20. HERRERA M B, FONSATO V, GATTI S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats[J]. J Cell Mol Med, 2010, 14(6B):1605-1618.
21. RANGHINO A, CANTALUPPI V, GRANGE C, et al. Endothelial progenitor cell-derived microvesicles improve neovascularization in murine model of hindlimbischemia[J]. Int J Immunopathol Pharmacol, 2012, 25(1):75-85.
22. CANTALUPPI V, GATTI S, MEDICA D, et al. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells[J]. Kidney Int, 2012, 82(4):412-427.
23. CANTALUPPI V, BIANCONE L, FIGLIOLINI F, et al. Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets[J]. Cell Transplant, 2012, 21(6):1305-1320.
24. SALLUSTIO F, COSTANTINO V, COX S N, et al. Human renal stem/progenitor cells repair tubular epithelial cell injury through TLR2-driven inhibin-A and microvesicle-shuttled decorin[J]. Kidney Int, 2013, 83(3):392-403.
25. WINYARD PJ, PRICE KL. Experimental renal progenitor cells:Repairing and recreating kidneys?[J]. Pediatr Nephrol, 2014, 29(4):665-672.
26. KATSMAN D, STACKPOLE E J, DOMIN D R, et al. Embryonic stem cell-derived microvesicles induce gene expression changes in Müller cells of the retina[J]. PLoS One, 2012, 7(11):e50417.
27. RADER D J, PARMACEK M S. Secreted miRNAs suppress atherogenesis[J]. Nat Cell Biol, 2012, 14(3):233-235.
28. KIM H S, CHOI D Y, YUN S J, et al. Proteomic analysis of microvesicles derived from human mesenchymal stem cells[J]. J Proteome Res, 2012, 11(2):839-849.
29. ANTHONY D F, SHIELS P G. Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs[J]. Transplant Res, 2013, 2(1):10-18.
30. ALVAREZ-ERVITI L, SEOW Y, YIN H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]. Nat Biotechnol, 2011, 29(4):341-345.

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