Abstract
The well-characterized curative effect of transplanted mesenchymal stem cells has been mainly attributed to their homing and subsequent differentiation for the repair and regeneration of damaged tissue. Adipose-derived mesenchymal stem cells (ADMSCs) are not only multipotent and plastic, but also abundant as they can be easily harvested with minimally invasive surgical techniques. This makes ADMSCs conducive for clinical applications. Recently, the secretory function of ADMSCs has been regarded as the primary mediator of MSC-based therapy. Exosomes are one kind of small cell extracellular membrane vesicles, which are primarily used to deliver cell-specific proteins, as well as nucleic acids secreted by various cell types. This review will introduce and characterize exosomes-derived ADMSCs (ADMSCs-Exo) and look at new therapies and prospective, including the limitations and outlook for therapeutic strategy. We will describe the latest research progress on myocardial repair, neuroprotection and neurotrophic effects, hepatic repair, renal repair, cutaneous repair, regeneration and other aspects using these cells.
Similar content being viewed by others
References
Akyurekli C, Le Y, Richardson RB, Fergusson D, Tay J, Allan DS (2015) A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev Rep 11:150–160
Arslan F et al (2013) Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3 K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 10:301–312
Bai Y et al (2018) Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem Biophys Res Commun 500:310–317. https://doi.org/10.1016/j.bbrc.2018.04.065
Behfar A et al (2010) Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction. J Am Coll Cardiol 56:721–734
Blazquez R, Sanchez-Margallo FM, de la Rosa O, Dalemans W, Vn Ãlvarez, Tarazona R, Casado JG (2014) Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells. Front Immunol. https://doi.org/10.3389/fimmu.2014.00556
Bonafede R et al (2016) Exosome derived from murine adipose-derived stromal cells: neuroprotective effect on in vitro model of amyotrophic lateral sclerosis. Exp Cell Res 340:150–158. https://doi.org/10.1016/j.yexcr.2015.12.009
Bryniarski K et al (2013) Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. J Allergy Clin Immunol 132:170–181
Burger D et al (2015) Human endothelial colony-forming cells protect against acute kidney injury: role of exosomes. Am J Pathol 185:2309–2323
Chawla LS, Eggers PW, Star RA, Kimmel PL (2014) Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 371:58–66
Chen Y-W, Tzeng J-I, Liu K-S, Yu S-H, Hung C-H, Wang J-J (2013) Systemic diphenidol reduces neuropathic allodynia and TNF-alpha overexpression in rats after chronic constriction injury. Neurosci Lett 552:62–65. https://doi.org/10.1016/j.neulet.2013.07.030
Chen H-H et al (2014a) Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. J Pineal Res 57:16–32. https://doi.org/10.1111/jpi.12140
Chen HH et al (2014b) Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury. Am J Transl Res 6:439
Chen KH et al (2016) Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget 7:74537–74556
Cheng AL et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:4–5
Cho BS, Jin OK, Ha DH, Yong WY (2018) Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther 9:187
Cui X, He Z, Liang Z, Chen Z, Wang H, Zhang J (2017) Exosomes from adipose-derived mesenchymal stem cells protect ischemic myocardium from ischemia/reperfusion injury via Wnt/Î2-catenin signaling pathway. J Cardiovasc Pharmacol 70:225
Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther Position Statement Cytotherapy 8:315
Dong S, Ye XD, Yuan Z, Xu LC, Xiao XS (2012) Relationship of apparent diffusion coefficient to survival for patients with unresectable primary hepatocellular carcinoma after chemoembolization. Eur J Radiol 81:472–477
Fruth S (2009) Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction. Cytotherapy 11:947–957
Guduric-Fuchs J, O’Connor A, Camp B, O’Neill CL, Medina RJ, Simpson DA (2012) Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genomics 13:357. https://doi.org/10.1186/1471-2164-13-357
Hare JM et al (2009) A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 54:2277–2286
Heo SH et al (2010) Apparent diffusion coefficient value of diffusion-weighted imaging for hepatocellular carcinoma: correlation with the histologic differentiation and the expression of vascular endothelial growth factor. Korean J Radiol 11:295–303
Kang HM, Huang S, Reidy K, Han SH, Chinga F, Susztak K (2016) Sox9 positive progenitor cells play a key role in renal tubule epithelial regeneration in mice. Cell Rep 14:861–871
Kiernan MC et al (2011) Amyotrophic lateral sclerosis. Lancet 377:942–955. https://doi.org/10.1016/S0140-6736(10)61156-7
Kim MH, Koh SO, Kim EJ, Jin SC, Na SW (2015) Incidence and outcome of contrast-associated acute kidney injury assessed with risk, injury, failure, loss, and end-stage kidney disease (RIFLE) criteria in critically ill patients of medical and surgical intensive care units: a retrospective study. BMC Anesthesiol 15(1):23
Kinoshita K et al (2015) Therapeutic potential of adipose-derived SSEA-3-positive muse cells for treating diabetic skin ulcers. Stem Cells Transl Med 4:146–155
Ko SF et al (2015) Adipose-derived mesenchymal stem cell exosomes suppress hepatocellular carcinoma growth in a rat model: apparent diffusion coefficient natural killer T-cell responses, and histopathological features. Stem Cells Int 2015:853506. https://doi.org/10.1155/2015/853506
Kumar et al (2015) Sox9 activation highlights a cellular pathway of renal repair in the acutely injured mammalian kidney. Cell Rep 12:1325–1338
Lee M, Ban J-J, Kim KY, Jeon GS, Im W, Sung J-J, Kim M (2016) Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro. Biochem Biophys Res Commun 479:434–439. https://doi.org/10.1016/j.bbrc.2016.09.069
Li H et al (2016) Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep 6:32993
Liang X, Zhang L, Wang S, Han Q, Zhao RC (2016) Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci 129:2182–2189
Lin R, Wang S, Zhao RC (2013) Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem 383:13–20
Lin KC et al (2016) Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury. Int J Cardiol 216:173–185
Ling et al (2008) Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res 18:500–507
Lu Z, Chen Y, Dunstan C, Roohani-Esfahani S, Zreiqat H (2017) Priming adipose stem cells with tumor necrosis factor-alpha preconditioning potentiates their exosome efficacy for bone regeneration. Tissue Eng Part A 23(21–22):1212–1220
Luo Q, Guo D, Liu G, Chen G, Hang M, Jin M (2017) Exosomes from MiR-126-overexpressing adscs are therapeutic in relieving acute myocardial ischaemic injury. Cell Physiol Biochem 44:2105–2116. https://doi.org/10.1159/000485949
Marote A, Teixeira FG, Mendespinheiro B, Salgado AJ (2016) MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential. Front Pharmacol 7:231
Mendez-Ferrer S et al (2009) Coordinated regulation of hematopoietic and mesenchymal stem cells in a bone marrow niche. Blood 114(22):3
Muhi A et al (2010) High-b-value diffusion-weighted MR imaging of hepatocellular lesions: estimation of grade of malignancy of hepatocellular carcinoma. J Magn Reson Imaging 30:1005–1011
Pacelli C et al (2011) Mitochondrial defect and PGC-1α dysfunction in parkin -associated familial Parkinson’s disease. BBA Mol Basis Dis 1812:1041–1053
Pickering JW, James MT, Palmer SC (2015) Acute kidney injury and prognosis after cardiopulmonary bypass: a meta-analysis of cohort studies. Am J Kidney Dis 65:283–293
Pu CM et al (2017) Adipose-derived stem cells protect skin flaps against ischemia/reperfusion injury via IL-6 expression. J Invest Dermatol 137:1353
Qu Y, Zhang Q, Cai X, Li F, Ma Z, Xu M, Lu L (2017) Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 21:2491–2502. https://doi.org/10.1111/jcmm.13170
Rodrigo SF et al (2013) Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up. J Cardiovasc Transl Res 6:816–825
Rossolallison J, Ward CJ (2015) Exosomes to the rescue. J Am Soc Nephrol 26:2303–2304
Sheng B, Wang X, Su B, Lee H-G, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in alzheimer’s disease. J Neurochem 120:419–429. https://doi.org/10.1111/j.1471-4159.2011.07581.x
Shin L, Peterson DA (2013) Human mesenchymal stem cell grafts enhance normal and impaired wound healing by recruiting existing endogenous tissue stem/progenitor cells. Stem Cells Transl Med 2:33–42
Sun CK et al (2011) Autologous transplantation of adipose-derived mesenchymal stem cells markedly reduced acute ischemia-reperfusion lung injury in a rodent model. J Transl Med 9(1):118
Taouli B, Koh DM (2010) Diffusion-weighted MR imaging of the liver. Radiology 254:47–66
Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. BBA Gen Subj 1820:940–948
Vyas N, Dhawan J (2017) Exosomes: mobile platforms for targeted and synergistic signaling across cell boundaries. Cell Mol Life Sci 74:1–10
Wang Y et al (2015) Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol 192:61–69
Wang K et al (2017) Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal MicroRNA-21. Stem Cells Transl Med 6:209–222. https://doi.org/10.5966/sctm.2015-0386
Wang L et al (2018) Author correction: exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. Sci Rep 7:13321
Xu Y, Luo F, Liu Y, Shi L, Lu X, Xu W, Liu Q (2015) Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial cells promotes cell proliferation associated with arsenite carcinogenesis. Arch Toxicol 89:1–12
Lou G, Song X, Fan Y, Wu S, Jing W, Zhi C, Liu Y (2015) Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol 8:1–11
Yang JJ et al (2012) Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits. Tohoku J Exp Med 226:231–241
Zhao H et al (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing m2 macrophages and beiging in white adipose tissues. Diabetes 67(2):235–247
Zhu F et al (2017) Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial cell dependent Sox9 activation. Oncotarget 8:70707–70726
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jianda Zhou and Ke Cao have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Fang, Y., Zhang, Y., Zhou, J. et al. Adipose-derived mesenchymal stem cell exosomes: a novel pathway for tissues repair. Cell Tissue Bank 20, 153–161 (2019). https://doi.org/10.1007/s10561-019-09761-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10561-019-09761-y