Skip to main content
SpringerLink
Log in

Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders

  • Feature Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can be isolated from various fetal and adult tissues. Over the fast decades, their multipotency, tissue reparative action, homing ability and immunoregulatory properties raised a great expectation in the field of stem cell and regenerative medicine that is being actively translated in a number of clinical trials worldwide. While MSC-based therapies have proven effectiveness in a numerous experimental models of human diseases and clinical studies including neurodegenerative disorders, there are accumulating evidences suggesting that the observed therapeutic effects in tissue regeneration is likely due to the paracrine actions of MSCs. Indeed, MSCs secrete trophic factors and cytokines (secretome) that have therapeutic relevance for the neurogenic, neuroprotective, angiogenic and anti-inflammatory/immunoregulatory activities. In addition, extracellular vesicles, such as microvesicles and exosomes, are proposed as key mediators of information transfer between different cells for tissue repair and regeneration. Although the underlying mechanism(s) of reparative action is not clear, evidences suggest that MSC secretome and microvesicles can recapitulate the beneficial effects as their cellular counterparts in tissue regeneration. Thus, secretome and microvesicles represent a promising candidate for a novel cell-free therapy for neurodegenerative diseases that has many advantages in overcoming the limitations and risks associated with the cell-based therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. AJ Friedenstein, RK Chailakhyan, NV Latsinik, et al., Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues: cloning in vitro and retransplantation in vivo, Transplantation, 17, 331 (1974).

    Article  PubMed  CAS  Google Scholar 

  2. MF Pittenger, AM Mackay, SC Beck, et al., Multilineage potential of adult human mesenchymal stem cells, Science, 284, 143 (1999).

    Article  PubMed  CAS  Google Scholar 

  3. P Bianco, PG Robey, PJ Simmons, Mesenchymal stem cells: revisiting history, concepts, and assays, Cell Stem Cell, 2, 313 (2008).

    Article  PubMed  CAS  Google Scholar 

  4. RE Schwartz, M Reyes, L Koodie, et al., Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells, J Clin Invest 109, 1291 (2002).

    PubMed  CAS  Google Scholar 

  5. J Sanchez-Ramos, S Song, F Cardozo-Pelaez, et al., Adult bone marrow stromal cells differentiate into neural cells in vitro, Exp Neurol, 164, 247 (2000).

    Article  PubMed  CAS  Google Scholar 

  6. Y Jiang, BN Jahagirdar, RL Reinhardt, et al., Pluripotency of mesenchymal stem cells derived from adult marrow, Nature, 418, 41 (2002).

    Article  PubMed  CAS  Google Scholar 

  7. EM Horwitz, K Le Blanc, M Dominici, et al., Clarification of the nomenclature for MSC: the international society for cellular therapy position statement, Cytotherapy, 7, 393 (2005).

    Article  PubMed  CAS  Google Scholar 

  8. B Sacchetti, A Funari, S Michienzi, et al., Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment, Cell, 131, 324 (2007).

    Article  PubMed  CAS  Google Scholar 

  9. M Dominici, K Le Blanc, I Mueller, et al., Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement, Cytotherapy, 8, 315 (2006).

    Article  PubMed  CAS  Google Scholar 

  10. M Gnecchi, LG Melo, Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium, Methods Mol Biol, 482, 281 (2009).

    Article  PubMed  CAS  Google Scholar 

  11. S Kim, JS Heo, HS Kim, et al., Isolation of mesenchymal stem cells from the mononuclear cells remaining in the bone marrow processing kit, Korean J Blood Transfusion, 21, 280 (2010).

    Google Scholar 

  12. W Wagner, REJ Feldmann, A Seckinger, et al., The heterogeneity of human mesenchymal stem cell preparations—evidence from simultaneous analysis of proteomes and transcriptomes, Exp Hematol, 34, 536 (2006).

    Article  PubMed  CAS  Google Scholar 

  13. S Mareddy, R Crawford, G Brooke, et al., Clonal isolation and characterization of bone marrow stromal cells from patients with osteoarthritis, Tissue Eng, 13, 819 (2007).

    Article  PubMed  CAS  Google Scholar 

  14. Y Xiao, S Mareddy, R Crawford, Clonal characterization of bone marrow derived stem cells and their application for bone regeneration, Int J Oral Sci, 2, 127 (2010).

    PubMed  Google Scholar 

  15. K Sivasubramaniyan, D Lehnen, R Ghazanfari, et al., Phenotypic and functional heterogeneity of human bone marrow- and amnion-derived MSC subsets, Ann NY Acad Sci, 1266, 94 (2012).

    Article  PubMed  Google Scholar 

  16. SP Bruder, NS Ricalton, RE Boynton, et al., Mesenchymal stem cell surface antigen SB-10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation, J Bone Mineral Res, 13, 655 (1998).

    Article  CAS  Google Scholar 

  17. RK Jaiswal, N Jaiswal, SP Bruder, et al., Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase, J Biol Chem, 275, 9645 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. F Barry, RE Boynton, B Liu, et al., Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components, Exp Cell Res, 268, 189 (2001).

    Article  PubMed  CAS  Google Scholar 

  19. AH Reddi, Role of morphogenetic proteins in skeletal tissue engineering and regeneration, Nature Biotech, 16, 247 (1998).

    Article  CAS  Google Scholar 

  20. T Gaur, CJ Lengner, H Hovhannisyan, et al., Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression, J Biol Chem, 280, 33132 (2005).

    Article  PubMed  CAS  Google Scholar 

  21. JH Kim, CS Cho, YH Choung, et al., Mechanical stimulation of mesenchymal stem cells for tissue engineering, Tissue Eng Reg Med, 6, 199 (2009).

    Google Scholar 

  22. S Makino, K Fukuda, S Miyoshi, et al., Cardiomyocytes can be generated from marrow stromal cells in vitro, J Clin Invest, 103, 697 (1999).

    Article  PubMed  CAS  Google Scholar 

  23. G Ferrari, G Cusella-De Angelis, M Coletta, et al., Muscle regeneration by bone marrow-derived myogenic progenitors, Science, 279, 1528 (1998).

    Article  PubMed  CAS  Google Scholar 

  24. Y Kashiwakura, Y Katoh, K Tamayose, et al., Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22alpha promoter: in vitro differentiation of putative smooth muscle progenitor cells of bone marrow, Circulation, 107, 2078 (2003).

    Article  PubMed  Google Scholar 

  25. GC Kopen, DJ Prockop, DG Phinney, Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains, Proc Natl Acad Sci USA, 96, 10711 (1999).

    Article  PubMed  CAS  Google Scholar 

  26. J Chen, Y Li, L Wang, et al., Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats, J Neurol Sci, 189, 49 (2001).

    Article  PubMed  CAS  Google Scholar 

  27. BE Petersen, WC Bowen, KD Patrene, et al., Bone marrow as a potential source of hepatic oval cells, Science, 284, 1168 (1999).

    Article  PubMed  CAS  Google Scholar 

  28. E Lagasse, H Connors, M Al-Dhalimy, et al., Purified hematopoietic stem cells can differentiate into hepatocytes in vivo, Nature Med, 6, 1229 (2000).

    Article  PubMed  CAS  Google Scholar 

  29. NR Blondheim, YS Levy, T Ben-Zur, et al., Human mesenchymal stem cells express neural genes, suggesting a neural predisposition, Stem Cells Dev, 15, 141 (2006).

    Article  PubMed  CAS  Google Scholar 

  30. D Woodbury, EJ Schwarz, DJ Prockop, et al., Adult rat and human bone marrow stromal cells differentiate into neurons, J Neurosci Res, 61, 364 (2000).

    Article  PubMed  CAS  Google Scholar 

  31. YS Levy, D Merims, H Panet, et al., Induction of neuronspecific enolase promoter and neuronal markers in differentiated mouse bone marrow stromal cells, J Mol Neurosci, 21, 121 (2003).

    Article  PubMed  CAS  Google Scholar 

  32. ML Khoo, B Shen, H Tao, et al., Long-term serial passage and neuronal differentiation capability of human bone marrow mesenchymal stem cells, Stem Cells Dev, 17, 883 (2008).

    Article  PubMed  CAS  Google Scholar 

  33. JL Spees, SD Olson, J Ylostalo, et al., Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma, Proc Natl Acad Sci USA, 100, 2397 (2003).

    Article  PubMed  CAS  Google Scholar 

  34. DG Phinney, DJ Prockop, Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views, Stem Cells, 25, 2896 (2007).

    Article  PubMed  Google Scholar 

  35. S Kim, HS Kim, E Lee, et al., In vivo hepatic differentiation potential of human cord blood-derived mesenchymal stem cells, Int J Mol Med, 27, 701 (2011).

    Article  PubMed  Google Scholar 

  36. S Wislet-Gendebien, P Leprince, G Moonen, et al., Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells, J Cell Sci, 116, 3295 (2003).

    Article  PubMed  CAS  Google Scholar 

  37. T Tondreau, L Lagneaux, M Dejeneffe, et al., Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation, Differentiation, 72, 319 (2004).

    Article  PubMed  CAS  Google Scholar 

  38. J Deng, BE Petersen, DA Steindler, et al., Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation, Stem Cells, 24, 1054 (2006).

    Article  PubMed  CAS  Google Scholar 

  39. LR Zhao, WM Duan, M Reyes, et al., Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats, Exp Neurol, 174, 11 (2002).

    Article  PubMed  Google Scholar 

  40. G Keilhoff, A Goihl, K Langnäse, et al., Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells, Eur J Cell Biol, 85, 11 (2006).

    Article  PubMed  CAS  Google Scholar 

  41. YS Levy, M Bahat-Stroomza, R Barzilay, et al., Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease, Cytotherapy, 10, 340 (2008).

    Article  PubMed  CAS  Google Scholar 

  42. NL Kennea, SN Waddington, J Chan, et al., Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype, Cell Cycle, 8, 1069 (2009).

    Article  PubMed  CAS  Google Scholar 

  43. B Neuhuber, G Gallo, L Howard, et al., Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype, J Neurosci Res, 77, 192 (2004).

    Article  PubMed  CAS  Google Scholar 

  44. Y Iso, JL Spees, C Serrano, et al., Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment, Biochem Biophys Res Commun, 354, 700 (2007).

    Article  PubMed  CAS  Google Scholar 

  45. L von Bahr, I Batsis, G Moll, et al., Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation, Stem Cells, 30, 1575 (2012).

    Article  CAS  Google Scholar 

  46. N Bertani, P Malatesta, G Volpi, et al., Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray, J Cell Sci, 118, 3925 (2005).

    Article  PubMed  CAS  Google Scholar 

  47. CB Choi, YK Cho, KV Prakash, et al., Analysis of neuron-like differentiation of human bone marrow mesenchymal stem cells, Biochem Biophys Res Commun, 350, 138 (2006).

    Article  PubMed  CAS  Google Scholar 

  48. T Tondreau, M Dejeneffe, N Meuleman, et al., Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells, BMC Genomics, 9, 166 (2008).

    Article  PubMed  CAS  Google Scholar 

  49. Y Li, J Chen, CL Zhang, et al., Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells, Glia, 49, 407 (2005).

    Article  PubMed  Google Scholar 

  50. PM Pimentel-Coelho, R Mendez-Otero, Cell therapy for neonatal hypoxicischemic encephalopathy, Stem Cells Dev, 19, 299 (2010).

    Article  PubMed  Google Scholar 

  51. YX Chao, BP He, SS Tay, Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson’s disease, J Neuroimmunol, 216, 39 (2009).

    Article  PubMed  CAS  Google Scholar 

  52. JK Lee, HK Jin, JS Bae, Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model, Neurosci Lett, 450, 136 (2009).

    Article  PubMed  CAS  Google Scholar 

  53. T Yasuhara, K Hara, M Maki, et al., Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxicischemic rats, J Cereb Blood Flow Metab, 28, 1804 (2008).

    Article  PubMed  CAS  Google Scholar 

  54. JS Jackson, JP Golding, C Chapon, et al., Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study, Stem Cell Res Ther, 1, 17 (2010).

    Article  PubMed  CAS  Google Scholar 

  55. S Kim, KA Chang, J Kim, et al., The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer’s disease mice, PLoS One, 7, e45757 (2012).

    Article  PubMed  CAS  Google Scholar 

  56. NK Venkataramana, SK Kumar, S Balaraju, et al., Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease, Transl Res, 155, 62 (2010).

    Google Scholar 

  57. OY Bang, JS Lee, PH Lee, et al., Autologous mesenchymal stem cell transplantation in stroke patients, Ann Neurol, 57, 874 (2005).

    Article  PubMed  Google Scholar 

  58. D Karussis, C Karageorgiou, A Vaknin-Dembinsky, et al., Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis, Arch Neurol, 67, 1187 (2010).

    Article  PubMed  Google Scholar 

  59. PH Lee, JE Lee, HS Kim, et al., A randomized trial of mesenchymal stem cells in multiple system atrophy, Ann Neurol, 72, 32 (2012).

    Article  PubMed  Google Scholar 

  60. R Pal, NK Venkataramana, A Bansal, et al., Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study, Cytotherapy, 11, 897 (2009).

    Article  PubMed  CAS  Google Scholar 

  61. NA Kishk, H Gabr, S Hamdy, et al., Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury, Neurorehabil Neural Repair, 24, 702 (2010).

    Article  PubMed  Google Scholar 

  62. J Tolar, AJ Nauta, MJ Osborn, et al., Sarcoma derived from cultured mesenchymal stem cells, Stem cells, 25, 371 (2007).

    Article  PubMed  CAS  Google Scholar 

  63. HS Sohn, JS Heo, HS Kim, et al., Duration of in vitro storage affects the key stem cell features of human bone marrowderived mesenchymal stem cells for clinical transplantation, Cytotherapy, In Press, (2013).

    Google Scholar 

  64. SM Devine, AM Bartholomew, N Mahmud, et al., Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion, Exp Hematol, 29, 244 (2001).

    Article  PubMed  CAS  Google Scholar 

  65. MA Hellmann, H Panet, Y Barhum, et al., Increased survival and migration of engrafted mesenchymal bone marrow stem cells in 6-hydroxydopamine-lesioned rodents, Neurosci Lett, 395, 124 (2006).

    Article  PubMed  CAS  Google Scholar 

  66. JR Chen, GY Cheng, CC Sheu, et al., Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke, J Anat, 213, 249 (2008).

    Article  PubMed  CAS  Google Scholar 

  67. HS Hong, J Lee, E Lee, et al., A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells, Nature Med, 15, 425 (2009).

    Article  PubMed  CAS  Google Scholar 

  68. H Yagi, A Soto-Gutierrez, B Parekkadan, et al., Mesenchymal stem cells: mechanisms of immunomodulation and homing, Cell Transplant, 19, 667 (2010).

    Article  PubMed  Google Scholar 

  69. D Woodbury, K Reynolds, IB Black, Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis, J Neurosci Res, 69, 908 (2002).

    Article  PubMed  CAS  Google Scholar 

  70. AA Mangi, N Noiseux, D Kong, et al., Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts, Nature Med, 9, 1195 (2003).

    Article  PubMed  CAS  Google Scholar 

  71. HS Kalluri, RJ Dempsey, Growth factors, stem cells, and stroke, Neurosurg Focus, 24, E14 (2008).

    Article  PubMed  Google Scholar 

  72. JR Munoz, BR Stoutenger, AP Robinson, et al., Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice, Proc Natl Acad Sci USA, 102, 18171 (2005).

    Article  PubMed  CAS  Google Scholar 

  73. AI Caplan, JE Dennis, Mesenchymal stem cells as trophic mediators, J Cell Biochem, 98, 1076 (2006).

    Article  PubMed  CAS  Google Scholar 

  74. L Crigler, RC Robey, A Asawachaicharn, et al., Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis, Exp Neurol, 198, 54 (2006).

    Article  PubMed  CAS  Google Scholar 

  75. VN Lama, L Smith, L Badri, et al., Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts, J Clin Invest, 117, 989 (2007).

    Article  PubMed  CAS  Google Scholar 

  76. MK Majumdar, MA Thiede, SE Haynesworth, et al., Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages, J Hematother Stem Cell Res, 9, 841 (2000).

    Article  PubMed  CAS  Google Scholar 

  77. T Kinnaird, E Stabile, MS Burnett, et al., Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms, Circulation, 109, 1543 (2004).

    Article  PubMed  CAS  Google Scholar 

  78. M Gnecchi, H He, OD Liang, et al., Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells, Nature Med, 11, 367 (2005).

    Article  PubMed  CAS  Google Scholar 

  79. L Timmers, SK Lim, F Arslan, et al., Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium, Stem Cell Res, 1, 129 (2007).

    Article  PubMed  CAS  Google Scholar 

  80. B Parekkadan, D van Poll, K Suganuma, et al., Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure, PLoS One, 2, e941 (2007).

    Article  PubMed  CAS  Google Scholar 

  81. GF Curley, M Hayes, B Ansari, et al., Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat, Thorax, 67, 496 (2012).

    Article  PubMed  Google Scholar 

  82. TJ Chuang, KC Lin, CC Chio, et al., Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats, J Trauma Acute Care Surg, 73, 1161 (2012).

    Article  PubMed  CAS  Google Scholar 

  83. DH Woo, SK Kim, HJ Lim, et al., Direct and indirect contribution of human embryonic stem cell-derived hepatocytelike cells to liver repair in mice, Gastroenterology, 142, 602 (2012).

    Article  PubMed  CAS  Google Scholar 

  84. J Ratajczak, K Miekus, M Kucia, et al., Embryonic stem cellderived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery, Leukemia, 20, 847 (2006).

    Article  PubMed  CAS  Google Scholar 

  85. H Valadi, K Ekström, A Bossios, et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells, Nature Cell Biol, 9, 654 (2007).

    Article  PubMed  CAS  Google Scholar 

  86. J Skog, T Würdinger, S van Rijn, et al., Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers, Nature Cell Biol, 10, 1470 (2008).

    Article  PubMed  CAS  Google Scholar 

  87. J Nilsson, J Skog, A Nordstrand, et al., Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer, Br J Cancer, 100, 1603 (2009).

    Article  PubMed  CAS  Google Scholar 

  88. C D’Souza-Schorey, JW Clancy, Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers, Genes Dev, 26, 1287 (2012).

    Article  PubMed  CAS  Google Scholar 

  89. S Gatti, S Bruno, MC Deregibus, et al., Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury, Nephrol Dial Transplant, 26, 1474 (2011).

    Article  PubMed  CAS  Google Scholar 

  90. S Bruno, C Grange, F Collino, et al., Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury, PLoS One, 7, e33115 (2012).

    Article  PubMed  CAS  Google Scholar 

  91. J He, Y Wang, S Sun, et al., Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model, Nephrol, 17, 493 (2012).

    Article  Google Scholar 

  92. RC Lai, F Arslan, MM Lee, et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury, Stem Cell Res, 4, 214 (2010).

    Article  PubMed  CAS  Google Scholar 

  93. MB Herrera, V Fonsato, S Gatti, et al., Human liver stem cellderived microvesicles accelerate hepatic regeneration in hepatectomized rats, J Cell Mol Med, 14, 1605 (2010).

    Article  PubMed  CAS  Google Scholar 

  94. F Collino, MC Deregibus, S Bruno, et al., Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs, PLoS One, 5, e11803 (2010).

    Article  PubMed  CAS  Google Scholar 

  95. HS Kim, DY Choi, SJ Yun, et al., Proteomic analysis of microvesicles derived from human mesenchymal stem cells, J Proteome Res, 11, 839 (2012).

    Article  PubMed  CAS  Google Scholar 

  96. L Alvarez-Erviti, Y Seow, H Yin, et al., Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes, Nature Biotech, 29, 341 (2011).

    Article  CAS  Google Scholar 

  97. A Yuan, EL Farber, AL Rapoport, et al., Transfer of microRNAs by embryonic stem cell microvesicles, PLoS One, 4, e4722 (2009).

    Article  PubMed  CAS  Google Scholar 

  98. CA Ribeiro, AJ Salgado, JS Fraga, et al., The secretome of bone marrow mesenchymal stem cells-conditioned media varies with time and drives a distinct effect on mature neurons and glial cells (primary cultures), J Tissue Eng Regen Med, 5, 668 (2011).

    Article  PubMed  CAS  Google Scholar 

  99. CA Ribeiro, JS Fraga, M Grãos, et al., The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations, Stem Cell Res Ther, 3, 18 (2012).

    Article  PubMed  CAS  Google Scholar 

  100. AP Horn, A Bernardi, R Luiz Frozza, et al., Mesenchymal stem cell-conditioned medium triggers neuroinflammation and reactive species generation in organotypic cultures of rat hippocampus, Stem Cells Dev, 20, 1171 (2011).

    Article  PubMed  CAS  Google Scholar 

  101. CP Chang, CC Chio, CU Cheong, et al., Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury, Clin Science, 124, 165 (2013).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Hyun Ok Kim, Seong-Mi Choi & Han-Soo Kim

  2. Cell Therapy Center, Yonsei University Health System, Seoul, 120-752, Korea

    Hyun Ok Kim & Han-Soo Kim

Authors
  1. Hyun Ok Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seong-Mi Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Han-Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Han-Soo Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H.O., Choi, SM. & Kim, HS. Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Eng Regen Med 10, 93–101 (2013). https://doi.org/10.1007/s13770-013-0010-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-013-0010-7

Key words

Search

Navigation