The Pros and Cons of Mesenchymal Stem Cell-Based Therapies

Aleksandra Musiał-Wysocka, Marta Kot, Marcin Majka, Aleksandra Musiał-Wysocka, Marta Kot, Marcin Majka

Abstract

The need to search for new, alternative treatments for various diseases has prompted scientists and physicians to focus their attention on regenerative medicine and broadly understood cell therapies. Currently, stem cells are being investigated for their potentially widespread use in therapies for many untreatable diseases. Nowadays modern treatment strategies willingly use mesenchymal stem cells (MSCs) derived from different sources. Researchers are increasingly aware of the nature of MSCs and new possibilities for their use. Due to their properties, especially their ability to self-regenerate, differentiate into several cell lineages and participate in immunomodulation, MSCs have become a promising tool in developing modern and efficient future treatment strategies. The great potential and availability of MSCs allow for their various clinical applications in the treatment of many incurable diseases. In addition to their many advantages and benefits, there are still questions about the use of MSCs. What are the mechanisms of action of MSCs? How do they reach their destination? Is the clinical use of MSCs safe? These are the main questions that arise regarding MSCs when they are considered as therapeutic tools. The diversity of MSCs, their different clinical applications, and their many traits that have not yet been thoroughly investigated are sources of discussions and controversial opinions about these cells. Here, we reviewed the current knowledge about MSCs in terms of their therapeutic potential, clinical effects and safety in clinical applications.

Keywords: engraftment; immunomodulatory properties; mesenchymal stem cells; somatic cell therapy; transplantation.

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1.
Fig. 1.
Mesenchymal stem cells sources.
Fig. 2.
Fig. 2.
Schematic of leukocyte transmigration through the endothelium. It is supposed that MSCs migration occurs in a similar manner. The graphic was prepared using modified art elements from Servier Medical Art, found at https://smart.servier.com.

References

    1. Sarukhan A, Zanotti L, Viola A. Mesenchymal stem cells: myths and reality. Swiss Med Wkly. 2015;145:1–11.
    1. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells -current trends and future prospective. Biosci Rep Biosci Reports. 2015;35(2):1–18.
    1. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Keating A, Prockop DJ, Horwitz EM. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317.
    1. Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L. Immunological characterization of multipotent mesenchymal stromal cells - the international society for cellular therapy (ISCT) working proposal. Cytotherapy. 2013;15(9):1054–1061.
    1. Giai Via A, Frizziero A, Oliva F. Biological properties of mesenchymal stem cells from different sources. Muscles Ligaments Tendons J. 2012;2(3):154–162.
    1. Pevsner-Fischer M, Levin S, Zipori D. The origins of mesenchymal stromal cell heterogeneity. Stem Cell Rev Rep. 2011;7(3):560–568.
    1. Maleki M, Ghanbarvand F, Behvarz MR, Ejtemaei M, Ghadirkhomi E. Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells. 2014;7(2):118–126.
    1. Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9(1):204.
    1. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Mag’Ayan A, Enikolopov GN, Frenette PS. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829–834.
    1. Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, Blake J, Schwager C, Eckstein V, Ansorge W, Ho AD. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 2005;33(11):1402–1416.
    1. Bianco P, Cao X, Frenette P, Mao J, Robey P, Simmons P, Wang C. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013;19(1):35–42.
    1. Im G I, Shin YW, Lee KB. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthr Cartil. 2005;13(10):845–853.
    1. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy. 2005;7(5):393–395.
    1. De Souza Fernandez T, De C, Fernandez S. Mesenchymal stem cells: biological characteristics and potential clinical applications for haematopoietic stem cell transplantation. In: M. Tomizawa M (Ed.), pluripotent stem cells - from the bench to the clinic. IntechOpen. 2016;3:495–519.
    1. L Ramos T, Sánchez-Abarca LI, Muntión S, Preciado S, Puig N, López-Ruano G, Hernández-Hernández Á, Redondo A, Ortega R, Rodríguez C, Sánchez-Guijo F, del Cañizo C. MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun Signal. 2016;14:2.
    1. Szabó GV, Kövesd Z, Cserepes J, Daróczy J, Belkin M, Acsády G. Peripheral blood-derived autologous stem cell therapy for the treatment of patients with late-stage peripheral artery disease-results of the short- and long-term follow-up. Cytotherapy. 2013;15(10):1245–1252.
    1. Secco M, Zucconi E, Vieira NM, Fogaça LL, Cerqueira A, Carvalho MD, Jazedje T, Okamoto OK, Muotri AR, Zatz M. Multipotent stem cells from umbilical cord: cord is richer than blood! Stem Cells. 2008;26(1):146–150.
    1. Bongso A, Fong CY. The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s jelly of the human umbilical cord. Stem Cell Rev Rep. 2013;9(2):226–240.
    1. Murray IR, West CC, Hardy WR, James AW, Park TS, Nguyen A, Tawonsawatruk T, Lazzari L, Soo C, Péault B. Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci. 2014;71(8):1353–1374.
    1. Richardson SM, Kalamegam G, Pushparaj PN, Matta C, Memic A, Khademhosseini A, Mobasheri R, Poletti FL, Hoyland JA, Mobasheri A. Mesenchymal stem cells in regenerative medicine: focus on articular cartilage and intervertebral disc regeneration. Methods. 2016;99:69–80.
    1. Wagner W, Bork S, Horn P, Krunic D, Walenda T, Diehlmann A, Benes V, Blake J, Huber FX, Eckstein V, Boukamp P, Ho AD. Aging and replicative senescence have related effects on human stem and progenitor cells. Plos One. 2009;4(6):e5846, 1–13.
    1. Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008;129(3):163–173.
    1. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45:e54.
    1. Wang LT, Ting CH, Yen ML, Liu KJ, Sytwu HK, Wu KK, Yen BL. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trias. J Biomed Sci. 2016;23(1):76–89.
    1. Prasad VK, Lucas KG, Kleiner GI, Talano JA, Jacobsohn D, Broadwater G, Monroy R, Kurtzberg J. Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant. 2011;17(4):534–541.
    1. Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154(5):1334–1342.
    1. Musialek P, Mazurek A, Jarocha D, Tekieli L, Szot W, Kostkiewicz M, Banys RP, Urbanczyk M, Kadzielski A, Trystula M, Kijowski J, Zmudka K, Podolec P. Myocardial regeneration strategy using Wharton’s jelly mesenchymal stem cells as an offthe-shelf “unlimited” therapeutic agent: results from the acute myocardial infarction first-in-man study. Adv Intervent Cardiol. 2015;11:100–107.
    1. Gojo S, Gojo N, Takeda Y, Mori T, Abe H, Kyo S, Hata JI, Umezawa A. In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Exp Cell Res. 2003;288(1):51–59.
    1. La Greca A, Solari C, Furmento V, Lombardi A, Biani MC, Aban C, Moro L, García M, Guberman AS, Sevlever GE, Miriuka SG, Luzzani C. Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells acquire a stromal modulatory proteomic pattern during differentiation. Exp Mol Med. 2018;50(9):119–131.
    1. Sabin K, Kikyo N. Microvesicles as mediators of tissue regeneration. Transl Res. 2014;163(4):286–295.
    1. Bobis-Wozowicz S, Kmiotek K, Kania K, Karnas E, Labedz-Maslowska A, Sekula M, Kedracka-Krok S, Kolcz J, Boruczkowski D, Madeja Z, Zuba-Surma EK. Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles. J Mol Med. 2017;95(2):205–220.
    1. Vonk LA, van Dooremalen SF, Liv N, Klumperman J, Coffer PJ, Saris DBF, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics. 2018;8(4):906–920.
    1. Pezzi A, Amorin B, Laureano Á, Valim V, Dahmer A, Zambonato B, Sehn F, Wilke I, Bruschi L, Lima da Silva MA, Filippi-Chiela E, Silla L. Effects of hypoxiain long term in vitro expansion of human bone marrow derived mesenchymal stem cells. J Cell Biochem. 2017;118(10):3072–3079.
    1. Stubbendorff M, Neofytou E, Deuse T, Mattutat D, Lange C, Reichenspurner H, Robbins RC, Beygui RE, Volk HD, Schrepfer S. Impact of donor age on biological and immunogenic propertiesof mesenchymal stroma cells. Arch Med Res. 2015;3:1–24.
    1. Siegel G, Kluba T, Hermanutz-Klein U, Bieback K, Northoff K, Schäfer R. Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells. BMC Medicine. 2013;11:146–166.
    1. Yukawa H, Watanabe M, Kaji N, Okamoto Y, Tokeshi M, Miyamoto Y, Noguchi H, Baba Y, Hayashi S. Monitoring transplanted adipose tissue-derived stem cells combined with heparin in the liver by fluorescence imaging using quantum dots. Biomaterials. 2012;33(7):2177–2186.
    1. Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P. MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood. 2007;109(9):4055–4063.
    1. Rombouts WJC, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia. 2003;17(1):160–170.
    1. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 2003;57(1):11–20.
    1. 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.
    1. De Becker A, Van Hummelen P, Bakkus M, Vande Broek I, De Wever J, De Waele M, Van Riet I. Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica. 2007;92(4):440–449.
    1. Shi M, Li J, Liao L, Chen B, Li B, Chen L, Jia H, Zhao RC. Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica. 2007;92(7):897–904.
    1. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, Mantovani A, Melillo G, Sica A. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med. 2003;198(9):1391–1402.
    1. Bobis-Wozowicz S, Miekus K, Wybieralska E, Jarocha D, Zawisz A, Madeja Z, Majka M. Genetically modified adipose tissue-derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice. Exp Hematol. 2011;39(6):686–696.e4.
    1. Kilpinen L, Tigistu-Sahle F, Oja S, Greco D, Parmar A, Saavalainen P, Nikkilä J, Korhonen M, Lehenkari P, Käkelä R, Laitinen S. Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality. J Lipid Res. 2013;54(3):622–635.
    1. Pereira RF, O’Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ. Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci. 1998;95(3):1142–1147.
    1. Akiyama Y, Radtke C, Honmou O, Kocsis JD. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia. 2002;39(3):229–236.
    1. Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. I.v. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Neuroscience. 2005;136(1):161–169.
    1. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5(1):54–63.
    1. Schrepfer S, Deuse T, Reichenspurner H, Fischbein MP, Robbins RC, Pelletier MP. Stem cell transplantation: the lung barrier. Transplant Proc. 2007;39(2):573–576.
    1. Erkers T, Kaipe H, Nava S, Mollde´n P, Gustafsson B, Axelsson R, Ringden O. Treatment of severe chronic Graft-Versus-Host disease with decidual stroma cells and tracking with 111Indium radiolabeling. Stem Cells Dev. 2015;24(2):253–263.
    1. Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, Saghari M, Malekzadeh R. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38(7):961–967.
    1. Walczak P, Zhang J, Gilad AA, Kedziorek DA, Ruiz-Cabello J, Young RG, Pittenger MF, Van Zijl PCM, Huang J, Bulte JWM. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke. 2008;39(5):1569–1574.
    1. Wysoczynki M, Khan A, Bolli R. New paradigms in cell therapy. Circ Res. 2018;123(2):138–158.
    1. Zhang D, Fan GC, Zhou X, Zhao T, Pasha Z, Xu M, Zhu Y, Ashraf M, Wang Y. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol. 2008;44(2):281–292.
    1. Segers VFM, Van Riet I, Andries LJ, Lemmens K, Demolder MJ, Becker AJML De, Kockx MM, Keulenaer GW, De Vincent FM, Riet I Van, Andries LJ, Demolder MJ, Becker AJML, De Mark M, De Keulenaer GW. Regulation and function of stem cells in the cardiovascular system. Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol. 2005;290:1370–1377.
    1. Docheva D, Popov C, Mutschler W, Schieker M. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. Alternative names and criteria. J Cell Mol Med. 2007;11(1):21–38.
    1. Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Publ Gr. 2010;11(9):633–643.
    1. Fox JM, Chamberlain G, Ashton BA, Middleton J. Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haemat. 2007;137(4):491–502.
    1. Heng YW, Koh CG. Actin cytoskeleton dynamics and the cell division cycle. Int J Biochem Cell Biol. 2010;42(10):1622–1633.
    1. Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and tracking. Stem Cells Int. 2013;2013:130763.
    1. Natsu K, Ochi M, Mochizuki Y, Hachisuka H, Yanada S, Yasunaga Y. Allogeneic bone marrow-derived mesenchymal stromal cells promote the regeneration of injured skeletal muscle without differentiation into myofibers. Tissue Eng. 2004;10(7–8):1093–1112.
    1. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005;33(2):145–152.
    1. Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F. Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008;15(10):730–738.
    1. Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood. 2006;108(12):3938–3944.
    1. Kunter U, Rong S, Boor P, Eitner F, Muller-Newen G, Djuric Z, van Roeyen CR, Konieczny A, Ostendorf T, Villa L, Milovanceva-Popovska M, Kerjaschki D, Floege J. Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol. 2007;18(6):1754–1764.
    1. Muller WA. Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol Mech Dis. 2011;6(1):323–344.
    1. Labrousse AM, Zappaterra MD, Rube DA, Bliek V Der, Cell M, Sesaki H, Jensen RE, Biol JC, Arimura S, Tsutsumi N, Natl P, et al. Cell migration: integrating signals from front to back. Science. 2003;302(5651):1704–1709.
    1. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells. 2006;24(4):1030–1041.
    1. Leibacher J, Henschler R. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res Ther. 2016;7(7):1–12.
    1. Kortesidis A, Zannettino A, Isenmann S, Shi S, Lapidot T, Gronthos S. Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood. 2005;105(10):3793–3801.
    1. Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Stem Cells. 2003;101(9):3722–3729.
    1. Nicola MD, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838–3843.
    1. De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A, Pascual CY, Aller MA, Arias J, Arnalich-Montiel F. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med. 2012;12(5):574–591.
    1. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–1822.
    1. Meisel R, Zibert A, Laryea M, Göbel M, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradation. Blood. 2004;103(12):4619–4621.
    1. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, Carosella ED, Deschaseaux F. 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. Stem Cells. 2008;26(1):212–222.
    1. Ding DC, Chou HL, Chang YH, Hung WT, Liu HW, Chu TY. Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stromaderived stem cells. Cell Transplant. 2016;25(2):217–228.
    1. Ristich V, Liang S, Zhang W, Wu J, Horuzsko A. Tolerization of dendritic cells by HLA-G. Eur J Immunol. 2005;35(4):1133–1142.
    1. Kim JH, Jo CH, Kim HR, Hwang Y. Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue. Stem Cells Int. 2018;2018:8429042, 1–12.
    1. Sheshgiri R, Rouas-Freiss N, Rao V, Butany J, Ramzy D, Krawice-Radanne I, Ross HJ, Carosella ED, Delgado DH. Myocardial HLA-G reliably indicates a low risk of acute cellular rejection in heart transplant recipients. J Heart Lung Transplant. 2008;27(5):522–527.
    1. Lanza F, Campioni D, Mauro E, Pasini A, Rizzo R. Immunosuppressive properties of mesenchymal stromal cells. Adv Stem Cell Res Chapt. 12. Ed: The Springer 2012;12:281–301.
    1. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A. Human mesenchymal stem cells modulate B-cell functions. Mult Scler. 2006;107(1):367–372.
    1. Kovacsovics-Bankowski M, Streeter PR, Mauch KA, Frey MR, Raber A, van t Hof W, Deans R, Maziarz RT. Clinical scale expanded adult pluripotent stem cells prevent graft-versus-host disease. Cell Immunol. 2009;255(1–2):55–60.
    1. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Rachmilewitz J, Galun E, Rachmilewitz J. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2010;105(5):2214–2219.
    1. Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F. The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol. 2008;251(2):131–136.
    1. Dazzi F, Marelli-Berg FM. Mesenchymal stem cells for graft-versus-host disease: close encounters with T cells. Eur J Immunol. 2008;38(6):1479–1482.
    1. Tse W, Pendleton J, Beyer W, Egalka M, Guinan E. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 2003;172(5):389–397.
    1. Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ. Safety of cell therapy with mesenchymal stromal cells (safecell): a systematic review and meta-analysis of clinical trials. Plos One. 2012;7(10):e47559, 1–21.
    1. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JWM, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects pf mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2011;67(10):1187–1194.
    1. Kim JS, Lee JH, Kwon O, Cho JH, Choi JY, Park SH, Kim CD, Kim YJ, Kim YL. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy. Kidney Res Clin Pract. 2017;36(2):200–204.
    1. Swaminathan M, Stafford-Smith M, Chertow GM, Warnock DG, Paragamian V, Brenner RM, Lellouche F, Fox-Robichaud A, Atta MG, Melby S, Mehta RL, Wald R, Verma S, Mazer CD; ACT-AKI investigators. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol. 2017;29(1):260–267.
    1. Tatsumi K, Ohashi K, Matsubara Y, Kohori A, Ohno T, Kakidachi H, Horii A, Kanegae K, Utoh R, Iwata T, Okano T. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism. Biochem Biophys Res Commun. 2013;431(2):203–209.
    1. Wu Z, Zhang S, Zhou L, Cai J, Tan J, Gao X, Zeng Z, Li D. Thromboembolism induced by umbilical cord mesenchymal stem cell infusion: a report of two cases and literature review. Transplant Proc. 2017;49(7):1656–1658.
    1. Asif S, Ekdahl KN, Fromell K, Gustafson E, Barbu A, Le Blanc K, Nilsson B, Teramura Y. Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes. Acta Biomater. 2016;35:194–205.
    1. Fiedler T, Rabe M, Mundkowski RG, Oehmcke-Hecht S, Peters K. Adipose-derived mesenchymal stem cells release microvesicles with procoagulant activity. Int J Biochem Cell Biol. 2018;100:49–53.
    1. Kassem M. Mesenchymal stem cells: biological characteristics and potential clinical applications. Cloning Stem Cells. 2004;6(4):369–374.
    1. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol. 2006;7:14.
    1. Røsland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lønning PE, Bjerkvig R, Schichor C. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009;69(13):5331–5339.
    1. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25(2):371–379.
    1. Chen G, Yue A, Ruan Z, Yin Y, Wang R, Ren Y, Zhu L. Monitoring the biology stability of human umbilical cord-derived mesenchymal stem cells during long-term culture in serum-free medium. Cell Tissue Bank. 2014;15(4):513–521.
    1. Bellagamba BC, Abreu BR, Grivicich I, Markarian CF, Chem E, Camassola M, Nardi NB, Dihl RR. Human mesenchymal stem cells are resistant to cytotoxic and genotoxic effects of cisplatin in vitro. Genet Mol Biol. 2016;39(1):129–134.
    1. Yubo M, Yanyan L, Li L, Tao S, Bo L, Lin C. Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: a meta-analysis. Plos One. 2017;12(4):e0175449: 1–16.
    1. Hatzistergos KE, Blum A, Ince T, Grichnik J, Hare JM. What is the oncologic risk of stem cell treatment for heart disease? Circ. Res. 2012;108(11):1300–1303.
    1. Barkholt L, Flory E, Jekerle V, Lucas-Samuel S, Ahnert P, Bisset L, Büscher D, Fibbe W, Foussat A, Kwa M, Lantz O, Mačiulaitis R, Palomäki T, Schneider CK, Sensebé L, Tachdjian G, Tarte K, Tosca L, Salmikangas P. Risk of tumorigenicity in mesenchymal stromal cell-based therapies--bridging scientific observations and regulatory viewpoints. Cytotherapy. 2013;15(7):753–759.
    1. Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med. 2011;9(29):1479–1493.
    1. Suzuki K, Sun R, Origuchi M, Kanehira M, Takahata T, Itoh J, Umezawa A, Kijima H, Fukuda S, Saijo Y. Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med. 2011;17(7–8):579–587.
    1. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–563.
    1. Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer. 2010;127(10):2323–2333.
    1. Mathew E, Brannon AL, Del Vecchio AC, Garcia PE, Penny MK, Kane KT, Vinta A, Buckanovich RJ, di Magliano MP. Mesenchymal stem cells promote pancreatic tumor growth by inducing alternative polarization of macrophages. Neoplasia. 2016;18(3):142–151.
    1. Komarova S, Roth J, Alvarez R, Curiel DT, Pereboeva L. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. J Ovarian Res. 2010;3(1):12.
    1. De Boeck A, Pauwels P, Hensen K, Rummens JL, Westbroek W, Hendrix A, Maynard D, Denys H, Lambein K, Braems G, Gespach C, Bracke M, de Wever O. Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut. 2013;62(4):550–560.
    1. Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. Plos One. 2009;4(4): e4992: 1–11.
    1. Jung Y, Kim JK, Shiozawa Y, Wang J, Mishra A, Joseph J, Berry JE, McGee S, Lee E, Sun H, Wang J, Jin T, Zhang H, Dai J, Krebsbach PH, Keller ET, Pienta KJ, Taichman RS. Recruitment of mesenchymal stem cells into prostate tumors promotes metastasis. Nat Commun. 2013;4:1795.
    1. Quante M, Tu SP, Tomita H, Gonda T, Sophie SW, Takashi S, Baik GH, Shibata W, Diprete B, Kelly S, Friedman R, Varro A, Tycko B, Wang TC. Bone marrow-derived myofibroblasts contribute to the growth MSC niche and promote tumour growth. Cancer Cell. 2012;19(2):257–272.
    1. Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res. 2007;74(2–3):72–84.
    1. Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010;29(2):249–261.
    1. Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64(23):8492–8495.
    1. Ren G, Zhao X, Wang Y, Zhang X, Chen X, Xu C, Yuan Z, Roberts AI, Zhang L, Zheng B, Wen T, Rabson AB, Tischfield JA, Shao C, Shi Y. CCR2-dependent recruitment of macrophages by tumor educated mesenchymal stromal cells promotes tumor development and is mimicked by TNF-alpha. Cell Stem Cell. 2013;11(6):812–824.
    1. Ramasamy R, Lam EWF, Soeiro I, Tisato V, Bonnet D, Dazzi F. Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia. 2007;21(2):304–310.
    1. Clarke MR, Imhoff FM, Baird SK. Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase-1 and -2. Mol Carcinog. 2015;54(10):1214–1219.
    1. Bruno S, Collino F, Iavello A, Camussi G. Effects of mesenchymal stromal cell-derived extracellular vesicles on tumor growth. Front Immunol. 2014;5:382.
    1. Wu S, Ju GQ, Du T, Zhu YJ, Liu GH. Microvesicles derived from human umbilical cord Wharton’s jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. Plos One. 2013;8(4):1–12.
    1. Ertaş G, Ural E, Ural D, Aksoy A, Kozdağ G, Gacar G, Karaöz E. Comparative analysis of apoptotic resistance of mesenchymal stem cells isolated from human bone marrow and adipose tissue. Sci World J. 2012;2012:105698:1–8.
    1. Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15(11):1009–1016.
    1. Von Bahr L, Batsis I, Moll G, Hägg M, Szakos A, Sundberg B, Uzunel M, Ringden O, Le Blanc K. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells. 2012;30(7):1575–1578.
    1. Mäkelä T, Takalo R, Arvola O, Haapanen H, Yannopoulos F, Blanco R, Ahvenjrvi L, Kiviluoma K, Kerkel E, Nystedt J, Juvonen T, Lehenkari P. Safety and biodistribution study of bone marrow-derived mesenchymal stromal cells and mononuclear cells and the impact of the administration route in an intact porcine model. Cytotherapy. 2015;17(4):392–402.
    1. Kim I, Bang SI, Lee SK, Park SY, Kim M, Ha H. Clinical implication of allogenic implantation of adipogenic differentiated adipose-derived stem cells. Stem Cells Transl Med. 2014;3(11):1312–1321.
    1. Huang XP, Sun Z, Miyagi Y, Kinkaid HM, Zhang L, Weisel RD, Li RK. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation. 2010;122(23):2419–2429.
    1. Cho PS, Messina DJ, Hirsh EL, Chi N, Goldman SN, Lo DP, Harris IR, Popma SH, Sachs DH, Huang CA. Immunogenicity of umbilical cord tissue derived cells. Blood. 2008;111(1):430–439.
    1. von Bonin M, Stölzel F, Goedecke A, Richter K, Wuschek N, Hölig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhäuser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009;43(3):245–251.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner