Therapeutic potential of mesenchymal stem cell-derived microvesicles.

Several studies have demonstrated that mesenchymal stem cells have the capacity to reverse acute and chronic kidney injury in different experimental models by paracrine mechanisms. This paracrine action may be accounted for, at least in part, by microvesicles (MVs) released from mesenchymal stem cells, resulting in a horizontal transfer of mRNA, microRNA and proteins. MVs, released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, are now recognized as being an integral component of the intercellular microenvironment. By acting as vehicles for information transfer, MVs play a pivotal role in cell-to-cell communication. This exchange of information between the injured cells and stem cells has the potential to be bi-directional. Thus, MVs may either transfer transcripts from injured cells to stem cells, resulting in reprogramming of their phenotype to acquire specific features of the tissue, or conversely, transcripts could be transferred from stem cells to injured cells, restraining tissue injury and inducing cell cycle re-entry of resident cells, leading to tissue self-repair. Upon administration with a therapeutic regimen, MVs mimic the effect of mesenchymal stem cells in various experimental models by inhibiting apoptosis and stimulating cell proliferation. In this review, we discuss whether MVs released from mesenchymal stem cells have the potential to be exploited in novel therapeutic approaches in regenerative medicine to repair damaged tissues, as an alternative to stem cell-based therapy.

[1]  G. Camussi,et al.  Microvesicles Derived from Mesenchymal Stem Cells Enhance Survival in a Lethal Model of Acute Kidney Injury , 2012, PloS one.

[2]  S. Lim,et al.  Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. , 2011, Regenerative medicine.

[3]  György Nagy,et al.  Cellular and Molecular Life Sciences REVIEW Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles , 2022 .

[4]  G. Camussi,et al.  Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  J. Lötvall,et al.  Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA , 2010, PloS one.

[6]  Luigi Biancone,et al.  Exosomes/microvesicles as a mechanism of cell-to-cell communication. , 2010, Kidney international.

[7]  Christian Weber,et al.  Microparticles: Protagonists of a Novel Communication Network for Intercellular Information Exchange , 2010, Circulation research.

[8]  G. Camussi,et al.  Stem Cells , Tissue Engineering and Hematopoietic Elements Stem Cells Derived from Human Amniotic Fluid Contribute to Acute Kidney Injury Recovery , 2010 .

[9]  A. Harris,et al.  New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. , 2010, Blood.

[10]  S. Mathivanan,et al.  Exosomes: extracellular organelles important in intercellular communication. , 2010, Journal of proteomics.

[11]  Luca Sterpone,et al.  Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs , 2010, PloS one.

[12]  P. Quesenberry,et al.  Stem cell plasticity revisited: the continuum marrow model and phenotypic changes mediated by microvesicles. , 2010, Experimental hematology.

[13]  Ronald G. Tompkins,et al.  Mesenchymal Stem Cells: Mechanisms of Immunomodulation and Homing , 2010, Cell transplantation.

[14]  P. Watkins,et al.  Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury , 2010, Hepatology.

[15]  Djuro Josic,et al.  Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. , 2010, Experimental hematology.

[16]  G. Camussi,et al.  Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats , 2009, Journal of cellular and molecular medicine.

[17]  M. Wewers,et al.  Monocyte Derived Microvesicles Deliver a Cell Death Message via Encapsulated Caspase-1 , 2009, PloS one.

[18]  F. Tögel,et al.  VEGF is a mediator of the renoprotective effects of multipotent marrow stromal cells in acute kidney injury , 2009, Journal of cellular and molecular medicine.

[19]  C. Théry,et al.  Membrane vesicles as conveyors of immune responses , 2009, Nature Reviews Immunology.

[20]  Alessandro Busca,et al.  Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. , 2009, Journal of the American Society of Nephrology : JASN.

[21]  Gen Suzuki,et al.  Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen. , 2009, American journal of physiology. Heart and circulatory physiology.

[22]  Jinkuk Kim,et al.  The role of mesenchymal stem cells in the functional improvement of chronic renal failure. , 2009, Stem cells and development.

[23]  D. Farber,et al.  Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles , 2009, PloS one.

[24]  Willem Stoorvogel,et al.  Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. , 2009, Blood.

[25]  Yao Zhang,et al.  Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure , 2009, Molecular Biology Reports.

[26]  P. Quesenberry,et al.  The Paradoxical Dynamism of Marrow Stem Cells: Considerations of Stem Cells, Niches, and Microvesicles , 2008, Stem Cell Reviews.

[27]  A. McMahon,et al.  Intrinsic epithelial cells repair the kidney after injury. , 2008, Cell stem cell.

[28]  N. Rouas-Freiss,et al.  Human Leukocyte Antigen‐G5 Secretion by Human Mesenchymal Stem Cells Is Required to Suppress T Lymphocyte and Natural Killer Function and to Induce CD4+CD25highFOXP3+ Regulatory T Cells , 2008, Stem cells.

[29]  P. Doevendans,et al.  Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. , 2008, Stem cell research.

[30]  G. Remuzzi,et al.  Insulin-like growth factor-1 sustains stem cell mediated renal repair. , 2007, Journal of the American Society of Nephrology : JASN.

[31]  Luigi Biancone,et al.  Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. , 2007, Blood.

[32]  L. Cantley,et al.  Stromal cells protect against acute tubular injury via an endocrine effect. , 2007, Journal of the American Society of Nephrology : JASN.

[33]  F. Miller Riding the waves: neural and nonneural origins for mesenchymal stem cells. , 2007, Cell stem cell.

[34]  S. E. Jacobsen,et al.  Potential risks of bone marrow cell transplantation into infarcted hearts. , 2007, Blood.

[35]  F. Djouad,et al.  Mesenchymal Stem Cells Inhibit the Differentiation of Dendritic Cells Through an Interleukin‐6‐Dependent Mechanism , 2007, Stem cells.

[36]  P. Boor,et al.  Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. , 2007, Journal of the American Society of Nephrology : JASN.

[37]  Arjun Deb,et al.  Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair , 2007, Proceedings of the National Academy of Sciences.

[38]  A. Caplan,et al.  Mesenchymal stem cells as trophic mediators , 2006, Journal of cellular biochemistry.

[39]  J Ratajczak,et al.  Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery , 2006, Leukemia.

[40]  G. Taraboletti,et al.  Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. , 2006, Neoplasia.

[41]  Linheng Li,et al.  Stem cell niche: structure and function. , 2005, Annual review of cell and developmental biology.

[42]  L. Hsiao,et al.  Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. , 2005, The Journal of clinical investigation.

[43]  J. Ingwall,et al.  Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells , 2005, Nature Medicine.

[44]  M. Pittenger,et al.  Human mesenchymal stem cells modulate allogeneic immune cell responses. , 2005, Blood.

[45]  G. Camussi,et al.  Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. , 2004, International journal of molecular medicine.

[46]  N. Perico,et al.  Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. , 2004, Journal of the American Society of Nephrology : JASN.

[47]  J. Lavail,et al.  The microvesicle as a vehicle for EMMPRIN in tumor–stromal interactions , 2004, Oncogene.

[48]  J. Greenberger,et al.  Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. , 2003, American journal of respiratory cell and molecular biology.

[49]  M. Ratajczak,et al.  Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV , 2003, AIDS.

[50]  Vincenza Dolo,et al.  Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. , 2002, The American journal of pathology.

[51]  H. Brühl,et al.  Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection , 2000, Nature Medicine.