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Review

Adipose-derived stromal/stem cells and extracellular vesicles for cancer therapy

&
Pages 67-78 | Received 23 Mar 2021, Accepted 07 Jul 2021, Published online: 21 Jul 2021

References

  • Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726–736.
  • Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–833.
  • Mitchell JB, McIntosh K, Zvonic S, et al. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells. 2006;24(2):376–385.
  • Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8:315–317.
  • Wankhade UD, Shen M, Kolhe R, et al. Advances in adipose-derived stem cells isolation, characterization, and application in regenerative tissue engineering. Stem Cells Int. 2016;2016:3206807.
  • Pittenger MF, Discher DE, Péault BM, et al. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22.
  • Si Z, Wang X, Sun C, et al. Adipose-derived stem cells: sources, potency, and implications for regenerative therapies. Biomed Pharmacother. 2019;114:108765.
  • Rajabzadeh N, Fathi E, Farahzadi R. Stem cell-based regenerative medicine. Stem Cell Investig. 2019;6:19.
  • Dubey NK, Mishra VK, Dubey R, et al. Revisiting the advances in isolation, characterization and secretome of adipose-derived stromal/stem cells. Int J Mol Sci. 2018;19(8):2200.
  • Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfus Med Hemother. 2016;43(4):268–274.
  • Fu Y, Karbaat L, Wu L, et al. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng Part B Rev. 2017;23(6):515–528.
  • Harrell CR, Jankovic MG, Fellabaum C, et al. Molecular mechanisms responsible for anti-inflammatory and immunosuppressive effects of mesenchymal stem cell-derived factors. Adv Exp Med Biol. 2019;1084:187–206.
  • [ cited 2021 Feb 25]. Available from: www.clinicaltrials.gov
  • Shukla L, Yuan Y, Shayan R, et al. Fat therapeutics: the clinical capacity of adipose-derived stem cells and exosomes for human disease and tissue regeneration. Front Pharmacol. 2020;11:158.
  • Zhang B, Yin Y, Lai RC, et al. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2013;23(11):1233–1244.
  • Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells. 2007;25(11):2896–2902.
  • Volarevic V, Markovic BS, Gazdic M, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci. 2018;15(1):36–45.
  • Berglund AK, Fortier LA, Antczak DF, et al. Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):288.
  • Shukla L, Morrison WA, Shayan R. Adipose-derived stem cells in radiotherapy injury: a new frontier. Front Surg. 2015;2:1.
  • Teufelsbauer M, Rath B, Moser D, et al. Interaction of adipose-derived stromal cells with breast cancer cell lines. Plast Reconstr Surg. 2019;144(2):207e–217e.
  • Varderidou-Minasian S, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics. 2020;10(13):5979–5997.
  • Zimmerlin L, Donnenberg VS, Pfeifer ME, et al. Stromal vascular progenitors in adult human adipose tissue. Cytometry A. 2010;77(1):22–30.
  • Marigo I, Dazzi F. The immunomodulatory properties of mesenchymal stem cells. Semin Immunopathol. 2011;33(6):593–602.
  • Vu B, Phan N, Pham P. Mesenchymal stem cells: vector for targeted cancer therapy. Prog Stem Cell. 2016;3(1):73–86.
  • Quan M, Kuang S. Exosomal secretion of adipose tissue during various physiological states. Pharm Res. 2020;37(11):221.
  • Kamal MM, Kassem DH. Therapeutic potential of wharton’s jelly mesenchymal stem cells for diabetes: achievements and challenges. Front Cell Dev Biol. 2020;8:16.
  • Goodwin HS, Bicknese AR, Chien SN, et al. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. Biol Blood Marrow Transplant. 2001;7(11):581–588.
  • Chang YJ, Shih DT, Tseng CP, et al. Disparate mesenchyme-lineage tendencies in mesenchymal stem cells from human bone marrow and umbilical cord blood. Stem Cells. 2006;24(3):679–685.
  • Bieback K, Kern S, Kluter H, et al. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004;22(4):625–634.
  • Arutyunyan I, Elchaninov A, Makarov A, et al. Umbilical cord as prospective source for mesenchymal stem cell-based therapy. Stem Cells Int. 2016;2016:6901286.
  • Shetty P, Cooper K, Viswanathan C. Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells. Asian J Transfus Sci. 2010;4(1):14–24.
  • Fong C, Chak L, Biswas A, et al. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev Rep. 2011;7(1):1–16.
  • Mazini L, Rochette L, Amine M, et al. Regenerative capacity of adipose derived stem cells (adscs), comparison with mesenchymal stem cells (MSCs). Int J Mol Sci. 2019;20:2530.
  • de Girolamo L, Lucarelli E, Alessandri G, et al. Italian Mesenchymal Stem Cell Group. Mesenchymal stem/stromal cells: a new “cells as drugs” paradigm. Efficacy and critical aspects in cell therapy. Curr Pharm Des. 2013;19(13):2459–2473.
  • Mehranfar S, Abdi Rad I, Mostafav E, et al. The use of stromal vascular fraction (SVF), platelet-rich plasma (PRP) and stem cells in the treatment of osteoarthritis: an overview of clinical trials. Artif Cells Nanomed Biotechnol. 2019;47(1):882–890.
  • Doucet C, Ernou I, Zhang YZ, et al. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol. 2005;205(2):228–236.
  • Lechanteur C, Briquet A, Giet O, et al. Clinical scale expansion of mesenchymal stromal cells: a large banking experience. J Transl Med. 2016;14(1):145.
  • Hanley PJ, Mei Z, Durett AG, et al. Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System. Cytotherapy. 2014;16:1048–1058.
  • Honczarenko M, Le Y, Swierkowski M, et al. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24:1030–1041.
  • Yoshimura K, Asano Y, Aoi N, et al. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010;16(2):169–175.
  • Eto H, Suga H, Matsumoto D, et al. Characterization of structure and cellular components of aspirated and excised adipose tissue. Plast Reconstr Surg. 2009;124(4):1087–1097.
  • Gurtner GC, Werner S, Barrandon Y, et al. Wound repair and regeneration. Nature. 2008;453(7193):314–321.
  • Spiekman M, van Dongen JA, Willemsen JC, et al. The power of fat and its adipose-derived stromal cells: emerging concepts for fibrotic scar treatment. J Tissue Eng Regen Med. 2017;11(11):3220–3235.
  • Zhang L, Zhang B, Liao B, et al. Platelet-rich plasma in combination with adipose-derived stem cells promotes skin wound healing through activating Rho GTPase-mediated signaling pathway. Am J Transl Res. 2019;11(7):4100–4112.
  • Lanao JM, Gutiérrez-Millán C, Colino CI. Cell-based drug delivery platforms. Pharmaceutics. 2020;13:1.
  • Pessina A, Bonomi A, Coccè V, et al. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One. 2011;6(12):e28321.
  • Pascucci L, Cocce V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262–270.
  • Cocce V, Farronato D, Brini AT, et al. Drug loaded gingival mesenchymal stromal cells (GinPa-MSCs) inhibit in vitro proliferation of oral squamous cell carcinoma. Sci Rep. 2017;7:9376.
  • Bonomi A, Coccè V, Cavicchini L, et al. Adipose tissue-derived stromal cells primed in vitro with paclitaxel acquire anti-tumor activity. Int J Immunopathol Pharmacol. 2013;26(1Suppl):33–41.
  • Brini AT, Cocce V, Ferreira LM, et al. Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel. Expert Opin Drug Deliv. 2016;13(6):789–798.
  • Nicolay NH, Lopez Perez R, Ruhle A, et al. Mesenchymal stem cells maintain their defining stem cell characteristics after treatment with cisplatin. Sci Rep. 2016;6:20035.
  • Gilazieva ZE, Tazetdinova LG, Arkhipova SS, et al. Effect of cisplatin on ultrastructure and viability of adipose-derived mesenchymal stem cells. BioNanoScience. 2016;6:534–539.
  • Li L, Guan Y, Liu H, et al. Silica nanorattledoxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS Nano. 2011;5(9):7462–7470.
  • Kamdje AHN, Etet PFS, Simo RT, et al. Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects. Cancer Biol Med. 2020;17(4):828–841.
  • Atiya H, Frisbie L, Pressimone C, et al. Mesenchymal stem cells in the tumor microenvironment. Adv Exp Med Biol. 2020;1234:31–42.
  • Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev. 2012;64(8):739–748.
  • Prindull G, Ben-Ishay Z, Ebell W, et al. CFU-F circulating in cord blood. Blut. 1987;54(6):351–359.
  • Sushilkumar R, Shabari S, Chandra V. Potential of mesenchymal stem cell-based application in cancer. Int J Hematol Oncol Stem Cell Res. 2015;9(2):95–103.
  • Kucerova L, Skolekova S, Matuskova M, et al. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells. BMC Cancer. 2013;9:13: 535.
  • Otsu K, Das S, Houser SD, et al. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells. Blood. 2009;113(18):4197–4205.
  • Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–1659.
  • Son BR, Marquez-Curtis LA, Kucia M, et al. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells. 2006;24(5):1254–1264.
  • Ramdasi S, Sarang S, Viswanathan C. Potential of mesenchymal stem cell based application in cancer. Int J Hematol Oncol Stem Cell Res. 2015;9(2):95–103.
  • Chulpanova DS, Kitaeva KV, Tazetdinova LG, et al. Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Front Pharmacol. 2018;9:259.
  • Borghese C, Casagrande N, Corona G, et al. Adipose-derived stem cells primed with paclitaxel inhibit ovarian cancer spheroid growth and overcome paclitaxel resistance. Pharmaceutics. 2020;12(5):401.
  • Mirzaei H, Salehi H, Oskuee RK, et al. The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model. Cancer Lett. 2018;419:30–39.
  • Cocce V, Balducci L, Falchetti ML, et al. Fluorescent immortalized human adipose derived stromal cells (hASCs-TS/GFP+) for studying cell drug delivery mediated by microvesicles. Anticancer Agents Med Chem. 2017;17(11):1578–1585.
  • Cheng S, Nethi SK, Rathi S, et al. Engineered mesenchymal stem cells for targeting solid tumors: therapeutic potential beyond regenerative therapy. J Pharmacol Exp Ther. 2019;370(2):231–241.
  • Melzer C, Rehn V, Yang Y, et al. Taxol-loaded MSC-derived exosomes provide a therapeutic vehicle to target metastatic breast cancer and other carcinoma cells. Cancers (Basel). 2019;11(6):798.
  • Crivelli B, Chlapanidas T, Perteghella S, et al. Mesenchymal stem/stromal cell extracellular vesicles: from active principle to next generation drug delivery system. J Control Release. 2017;262:104–117.
  • Wiklander OPB, Brennan MA, Lotvall J, et al. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med. 2019;11(492):eaav8521.
  • Melling GE, Carollo E, Conlon R, et al. The challenges and possibilities of extracellular vesicles as therapeutic vehicles. Eur J Pharm Biopharm. 2019;144:50–56.
  • Cai Y, Li J, Jia C, et al. Therapeutic applications of adipose cell-free derivatives: a review. Stem Cell Res Ther. 2020;11(1):312.
  • Zhang C, Wang T, Zhang L, et al. Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring. Stem Cell Res Ther. 2021;12(1):23.
  • Choi EW, Seo MK, Woo EY, et al. Exosomes from human adipose-derived stem cells promote proliferation and migration of skin fibroblasts. Exp Dermatol. 2018;27(10):1170–1172.
  • Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant. 2016;25(5):829–848.
  • Xu R, Rai A, Chen M, et al. Extracellular vesicles in cancer - implications for future improvements in cancer care. Nat Rev Clin Oncol. 2018;15(10):617–638.
  • Qiu H, Liu S, Wu K, et al. Prospective application of exosomes derived from adipose-derived stem cells in skin wound healing: a review. J Cosmet Dermatol. 2020;19(3):574–581.
  • Thery C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.
  • Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–1232.
  • de Jong B, Barros ER, Hoenderop JGJ, et al. Recent advances in extracellular vesicles as drug delivery systems and their potential in precision medicine. Pharmaceutics. 2020;12(11):1006.
  • Wolfram J, Ferrari M. Clinical cancer nanomedicine. Nano Today. 2019;25:85–98.
  • Yamamoto T, Kosaka N, Ochiya T. Latest advances in extracellular vesicles: from bench to bedside. Sci Technol Adv Mater. 2019;20(1):746–757.
  • Rai A, Greening DW, Chen M, et al. Exosomes derived from human primary and metastatic colorectal cancer cells contribute to functional heterogeneity of activated fibroblasts by reprogramming their proteome. Proteomics. 2019;19(8):e1800148.
  • Elsharkasy OM, Nordin JZ, Hagey DW, et al. Extracellular vesicles as drug delivery systems: why and how? Adv Drug Deliv Rev. 2020;159:332–343.
  • van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228.
  • Ferreira ADF, Gomes DA. Stem cell extracellular vesicles in skin repair. Bioengineering (Basel). 2018;6(1):4.
  • Antonyak MA, Cerione RA. Natl Acad Sci USA. Emerging picture of the distinct traits and functions of microvesicles and exosomes. Proc Natl Acad Sci USA. 2015;112(12):3589–3590.
  • Thomou T, Mori MA, Dreyfuss JM, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542(7642):450–455.
  • Tomuleasa C, Braicu C, Irimie A, et al. Nanopharmacology in translational hematology and oncology. Int J Nanomedicine. 2014;9:3465–3479.
  • Munteanu R, Onaciu A, Moldovan C, et al. Adipocyte-based cell therapy in oncology: the role of cancer-associated adipocytes and their reinterpretation as delivery platforms. Pharmaceutics. 2020;12(5):402.
  • Yim N, Ryu SW, Choi K, et al. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module. Nat Commun. 2016;22(7):12277.
  • Rohde E, Pachler K, Gimona M. Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing. Cytotherapy. 2019;21(6):581–592.
  • Brossa A, Fonsato V, Grange C, et al. Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo. Int J Cancer. 2020;147(6):1694–1706.
  • Yong T, Zhang X, Bie N, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat Commun. 2019;10(1):3838.
  • Scholl JN, de Fraga Dias A, Pizzato PR, et al. Characterization and antiproliferative activity of glioma-derived extracellular vesicles. Nanomed (Lond). 2020;15(10):1001–1018.
  • Wiklander OP, Nordin JZ, O’Loughlin A, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4:26316.
  • Yang -X-X, Sun C, Wang L, et al. New insight into isolation, identification techniques and medical applications of exosomes. J Control Release. 2019;308:119–129.
  • Harrell CR, Fellabaum C, Jovicic N, et al. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells. 2019;8(5):467.
  • Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells. 2019;8(12):1605.
  • Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35(4):851–858.
  • Qiu G, Zheng G, Ge M, et al. Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Res Ther. 2018;9(1):320.
  • Harrell CR, Jovicic N, Djonov V, et al. Therapeutic use of mesenchymal stem cell-derived exosomes: from basic science to clinics. Pharmaceutics. 2020;12(5):474.
  • Mendt M, Rezvani K, Shpall E. Mesenchymal stem cell-derived exosomes for clinical use. Bone Marrow Transplant. 2019;54(Suppl 2):789–792.
  • Leibacher J, Henschler R. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res Ther. 2016;7:7.
  • Zhuang WZ, Lin YH, Su LJ, et al. Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications. J Biomed Sci. 2021;28(1):28.
  • Geiger A, Walker A, Nissen E. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem Biophys Res Commun. 2015;467(2):303–309.
  • Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med. 2015;13:49.
  • Wang L, Hu L, Zhou X, et al. Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodelling. Sci Rep. 2017;7(1):13321.
  • Ren S, Chen J, Duscher D, et al. Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways. Stem Cell Res Ther. 2019;10(1):47.
  • Lopatina T, Bruno S, Tetta C, et al. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun Signal. 2014;12:26.
  • Lin R, Wang S, Zhao RC. Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem. 2013;383(1–2):13–20.
  • Takahara K, Ii M, Inamoto T, et al. microRNA-145 mediates the inhibitory effect of Adipose tissue-derived stromal cells on prostate cancer. Stem Cells Dev. 2016;25(17):1290–1298.
  • Pariset E, Agache V, Millet A. Extracellular vesicles: isolation methods. Adv Biosyst. 2017;1(5):e1700040.
  • Konoshenko MY, Lekchnov EA, Vlassov AV, et al. Isolation of extracellular vesicles: general methodologies and latest trends. Biomed Res Int. 2018;2018:8545347.
  • Gobin J, Muradia G, Mehic J, et al. Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell. Stem Cell Res Ther. 2021;12(1):127.
  • Kordelas L, Rebmann V, Ludwig AK, et al. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus host disease. Leukemia. 2014;28(4):970–973.
  • Andaloussi SEL, Mager I, Breakefield XO, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–357.
  • Pokharel D, Wijesinghe P, Oenarto V, et al. Deciphering cell-to-cell communication in acquisition of cancer traits: extracellular membrane vesicles are regulators of tissue biomechanics. OMICS. 2016;20(8):462–469.
  • Bliss SA, Sinha G, Sandiford OA, et al. Mesenchymal stem cell-derived exosomes stimulate cycling quiescence and early breast cancer dormancy in bone marrow. Cancer Res. 2016;76(19):5832–5844.
  • Del Fattore A, Luciano R, Saracino R, et al. Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells. Expert Opin Biol Ther. 2015;15(4):495–504.
  • Granneman JG. Delivery of DNA into adipocytes within adipose tissue. Adv Struct Saf Stud. 2008;423:191–195.
  • Tsai WC, Hsu SD, Hsu CS, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest. 2012;122(8):2884–2897.
  • Nakao K, Miyaaki H, Ichikawa T. Antitumor function of microRNA-122 against hepatocellular carcinoma. J Gastroenterol. 2014;49(4):589–593.
  • Lou G, Song X, Yang F, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.
  • O’Brien KP, Khan S, Gilligan KE, et al. Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379. Oncogene. 2018;37(16):2137–2149.
  • Khan S, Brougham CL, Ryan J, et al. miR-379 regulates cyclin B1 expression and is decreased in breast cancer. PLoS One. 2013;8(7):e68753.
  • Mills J, Capece M, Cocucci E, et al. Cancer-derived extracellular vesicle-associated micrornas in intercellular communication: one cell’s trash is another cell’s treasure. Int J Mol Sci. 2019;20(24):6109.
  • Robb KP, Fitzgerald JC, Barry F, et al. Mesenchymal stromal cell therapy: progress in manufacturing and assessments of potency. Cytotherapy. 2019;21(3):289–306.
  • Jossen V, van den Bos C, Eibl R, et al. Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges. Appl Microbiol Biotechnol. 2018;102(9):3981–3994.
  • Beckenkamp LR, da Fontoura DMS, Korb VG, et al. Immortalization of mesenchymal stromal cells by TERT affects adenosine metabolism and impairs their immunosuppressive capacity. Stem Cell Rev Rep. 2020;16(4):776–791.
  • Simonsen JL, Rosada C, Serakinci N, et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol. 2002;20(6):592–596.
  • Lee MK, Hande MP, Sabapathy K. Ectopic mTERT expression in mouse embryonic stem cells does not affect differentiation but confers resistance to differentiation- and stress-induced p53-dependent apoptosis. J Cell Sci. 2005;118:819–829.
  • Siska EK, Weisman I, Romano J, et al. Generation of an immortalized mesenchymal stem cell line producing a secreted biosensor protein for glucose monitoring. PLoS One. 2017;12(9):e0185498.

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