PROGRESS OF MESENCHYMAL STEM CELL-DERIVED Exosomes IN TISSUE REPAIR_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LIXiao , LIULingying ,  CHAIJiake

Department of Joint Bone Tumor Surgery, the First Affiliated Hospital of Anhui Medical University, Anhui Hefei, 230022, P. R. China;

Corresponding author：

CHAIJiake, Email: chaijk304@126.com

Keywords：

Mesenchymal stem cells; Exosomes; Paracrine; Tissue repair

DOI：

10.7507/1002-1892.20150049

Video：

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Objective To comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) derived exosomes (MSCs-exosomes) in tissue repair. Methods The literature about MSCs-exosomes in tissue repair was reviewed and analyzed. Results Exosomes are biologically active microvesicles released from MSCs which are loaded with functional proteins, RNA, and microRNA. Exosomes can inhibit apoptosis, stimulate proliferation, alter cell phenotype in tissue repair of several diseases through cell-to-cell communication. Conclusion MSCs-exosomes is a novel source for the treatment of tissue repair. Further research of MSCs-exosomes biofunction, paracellular transport, and treatment mechanism will help the transform to clinical application.

Citation： LIXiao, LIULingying, CHAIJiake. PROGRESS OF MESENCHYMAL STEM CELL-DERIVED Exosomes IN TISSUE REPAIR. Chinese Journal of Reparative and Reconstructive Surgery, 2015, 29(2): 234-238. doi: 10.7507/1002-1892.20150049 Copy

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2.	Katsuda T, Kosaka N, Takeshita F, et al. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics, 2013, 13(10-11):1637-1653.
3.	Salem HK, Thiemermann C. Mesenchymal stromal cells:current understanding and clinical status. Stem Cells, 2010, 28(3):585-596.
4.	Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem, 2006, 98(5):1076-1084.
5.	Ankrum J, Karp JM. Mesenchymal stem cell therapy:Two steps forward, one step back. Trends Mol Med, 2010, 16(5):203-209.
6.	Furlani D, Ugurlucan M, Ong L, et al. Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvasc Res, 2009, 77(3):370-376.
7.	Breitbach M, Bostani T, Roell W, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood, 2007, 110(4):1362-1369.
8.	Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem, 2003, 278(13):10963-10972.
9.	Simpson RJ, Jensen SS, Lim JW. Proteomic pro filing of exosomes:current perspectives. Proteomics, 2008, 8(19):4083-4099.
10.	Aliotta JM, Pereira M, Li M, et al. Stable cell fate changes in marrow cells induced by lung-derived microvesicles. Journal of Extracellular Vesicles, 2012, 1:1-13.
11.	Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles, 2014, 4:3.
12.	Corrado C, Raimondo S, Chiesi A, et al. Exosomes as intercellular signaling organelles involved in health and disease:basic science and clinical applications. Int J Mol Sci, 2013, 14(3):5338-5366.
13.	Tetta C, Ghigo E, Silengo L, et al. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine, 2013, 44(1):11-19.
14.	Dooner MS, Aliotta JM, Pimentel J, et al. Conversion potential of marrow cells into lung cells fluctuates with cytokine-induced cell cycle. Stem Cells Dev, 2008, 17(2):207-219.
15.	Pilkis SJ, El-Maghrabi MR, Pilkis J, et al. Inhibition of fructose-1, 6-bisphosphatase by fructose 2, 6-bisphosphate. J Biol Chem, 1981, 256(8):3619-3622.
16.	Chen TS, Lai RC, Lee MM, et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res, 2010, 38(1):215-224.
17.	Yin J, Xu K, Zhang J, et al. Wound-induced ATP release and EGF receptor activation in epithelial cells. J Cell Sci, 2007, 120(Pt 5):815-825.
18.	Jacobson KA. Introduction to adenosine receptors as therapeutic targets. Handb Exp Pharmacol, 2009, (193):1-24.
19.	Davies A, Simmons DL, Hale G, et al. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med, 1989, 170(3):637-654.
20.	Humphreys BD, Bonventre JV. Mesenchymal stemcells in acute kidney injury. Annu Rev Med, 2008, 59:311-325.
21.	Bruno S, Grange C, Deregibus MC, et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol, 2009, 20(5):1053-1067.
22.	Bruno S, Grange C, Collino F, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One, 2012, 7(3):e33115.
23.	Gatti S, Bruno S, Deregibus MC, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant, 2011, 26(5):1474-1483.
24.	He J, Wang Y, Sun S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton), 2012,17(5):493-500.
25.	Reis LA, Borges FT, Simões MJ, et al. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One, 2012, 7(9):e44092.
26.	Ranganath SH, Levy O, Inamdar MS, et al. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 2012, 10(3):244-258.
27.	Lai RC, Arslan F, Lee MM, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res, 2010, 4(3):214-222.
28.	Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome:a novel stem cell-based therapy for cardiovascular disease. Regen Med, 2011, 6(4):481-492.
29.	Honmou O, Onodera R, Sasaki M, et al. Mesenchymal stem cells:therapeutic outlook for stroke. Trends Mol Med, 2012, 18(5):292-297.
30.	Yu YM, Gibbs KM, Davila J, et al. MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. Eur J Neurosci, 2011, 33(9):1587-1597.
31.	Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells, 2012, 30(7):1556-1564.
32.	Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells, 2013, 31(12):2737-2746.
33.	Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep, 2013, 3:1197.
34.	Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol, 2008, 8(9):726-736.
35.	Parolini I, Federici C, Raggi C, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem, 2009, 284(49):34211-34222.
36.	Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated antiinflammatory drugs from the nasal region to the brain. Mol Ther, 2011, 19(10):1769-1779.
37.	Akyurekli C, Le Y, Richardson RB, et al. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev, 2014.[Epub ahead of print].
38.	Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 2011, 29(4):341-345.
39.	Kosaka N, Iguchi H, Yoshioka Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem, 2010, 285(23):17442-17452.
40.	Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles:nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci, 2009, 30(11):592-599.

1. Kuçi S, Kuçi Z, Latifi-Pupovci H, et al. Adult stem cells as an alternative source of multipotential (pluripotential) cells in regenerative medicine. Curr Stem Cell Res Ther, 2009, 4(2):107-117.
2. Katsuda T, Kosaka N, Takeshita F, et al. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics, 2013, 13(10-11):1637-1653.
3. Salem HK, Thiemermann C. Mesenchymal stromal cells:current understanding and clinical status. Stem Cells, 2010, 28(3):585-596.
4. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem, 2006, 98(5):1076-1084.
5. Ankrum J, Karp JM. Mesenchymal stem cell therapy:Two steps forward, one step back. Trends Mol Med, 2010, 16(5):203-209.
6. Furlani D, Ugurlucan M, Ong L, et al. Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvasc Res, 2009, 77(3):370-376.
7. Breitbach M, Bostani T, Roell W, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood, 2007, 110(4):1362-1369.
8. Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem, 2003, 278(13):10963-10972.
9. Simpson RJ, Jensen SS, Lim JW. Proteomic pro filing of exosomes:current perspectives. Proteomics, 2008, 8(19):4083-4099.
10. Aliotta JM, Pereira M, Li M, et al. Stable cell fate changes in marrow cells induced by lung-derived microvesicles. Journal of Extracellular Vesicles, 2012, 1:1-13.
11. Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles, 2014, 4:3.
12. Corrado C, Raimondo S, Chiesi A, et al. Exosomes as intercellular signaling organelles involved in health and disease:basic science and clinical applications. Int J Mol Sci, 2013, 14(3):5338-5366.
13. Tetta C, Ghigo E, Silengo L, et al. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine, 2013, 44(1):11-19.
14. Dooner MS, Aliotta JM, Pimentel J, et al. Conversion potential of marrow cells into lung cells fluctuates with cytokine-induced cell cycle. Stem Cells Dev, 2008, 17(2):207-219.
15. Pilkis SJ, El-Maghrabi MR, Pilkis J, et al. Inhibition of fructose-1, 6-bisphosphatase by fructose 2, 6-bisphosphate. J Biol Chem, 1981, 256(8):3619-3622.
16. Chen TS, Lai RC, Lee MM, et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res, 2010, 38(1):215-224.
17. Yin J, Xu K, Zhang J, et al. Wound-induced ATP release and EGF receptor activation in epithelial cells. J Cell Sci, 2007, 120(Pt 5):815-825.
18. Jacobson KA. Introduction to adenosine receptors as therapeutic targets. Handb Exp Pharmacol, 2009, (193):1-24.
19. Davies A, Simmons DL, Hale G, et al. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med, 1989, 170(3):637-654.
20. Humphreys BD, Bonventre JV. Mesenchymal stemcells in acute kidney injury. Annu Rev Med, 2008, 59:311-325.
21. Bruno S, Grange C, Deregibus MC, et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol, 2009, 20(5):1053-1067.
22. Bruno S, Grange C, Collino F, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One, 2012, 7(3):e33115.
23. Gatti S, Bruno S, Deregibus MC, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant, 2011, 26(5):1474-1483.
24. He J, Wang Y, Sun S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton), 2012,17(5):493-500.
25. Reis LA, Borges FT, Simões MJ, et al. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One, 2012, 7(9):e44092.
26. Ranganath SH, Levy O, Inamdar MS, et al. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell, 2012, 10(3):244-258.
27. Lai RC, Arslan F, Lee MM, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res, 2010, 4(3):214-222.
28. Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome:a novel stem cell-based therapy for cardiovascular disease. Regen Med, 2011, 6(4):481-492.
29. Honmou O, Onodera R, Sasaki M, et al. Mesenchymal stem cells:therapeutic outlook for stroke. Trends Mol Med, 2012, 18(5):292-297.
30. Yu YM, Gibbs KM, Davila J, et al. MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. Eur J Neurosci, 2011, 33(9):1587-1597.
31. Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells, 2012, 30(7):1556-1564.
32. Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells, 2013, 31(12):2737-2746.
33. Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep, 2013, 3:1197.
34. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol, 2008, 8(9):726-736.
35. Parolini I, Federici C, Raggi C, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem, 2009, 284(49):34211-34222.
36. Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated antiinflammatory drugs from the nasal region to the brain. Mol Ther, 2011, 19(10):1769-1779.
37. Akyurekli C, Le Y, Richardson RB, et al. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev, 2014.[Epub ahead of print].
38. Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 2011, 29(4):341-345.
39. Kosaka N, Iguchi H, Yoshioka Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem, 2010, 285(23):17442-17452.
40. Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles:nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci, 2009, 30(11):592-599.

Chinese Journal of Reparative and Reconstructive Surgery

PROGRESS OF MESENCHYMAL STEM CELL-DERIVED Exosomes IN TISSUE REPAIR

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