Inflammation and Hypoxia Negatively Impact the Survival and Immunosuppressive Properties of Mesenchymal Stromal Cells In Vitro

1 Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276, 71–74. ProckopDJ Marrow stromal cells as stem cells for nonhematopoietic tissues Science 1997 276 71 74 10.1126/science.276.5309.719082988 Search in Google Scholar

2 Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. 2006;(174):249–82. Beyer NardiN da Silva MeirellesL Mesenchymal stem cells: isolation, in vitro expansion and characterization Handb Exp Pharmacol 2006 174 249 82 10.1007/3-540-31265-X_11 Search in Google Scholar

3 Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010; 466, 829–834. Méndez-FerrerS MichurinaTV FerraroF MazloomAR MacArthurBD LiraSA ScaddenDT Ma’ayanA EnikolopovGN FrenettePS Mesenchymal and haematopoietic stem cells form a unique bone marrow niche Nature 2010 466 829 834 10.1038/nature09262314655120703299 Search in Google Scholar

4 Wei Q, Frenette PS. Niches for Hematopoietic Stem Cells and Their Progeny. Immunity 2018; 48, 632–648. WeiQ FrenettePS Niches for Hematopoietic Stem Cells and Their Progeny Immunity 2018 48 632 648 10.1016/j.immuni.2018.03.024610352529669248 Search in Google Scholar

5 Trounson A, McDonald C. Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell 2015; 17, 11–22. TrounsonA McDonaldC Stem Cell Therapies in Clinical Trials: Progress and Challenges Cell Stem Cell 2015 17 11 22 10.1016/j.stem.2015.06.00726140604 Search in Google Scholar

6 Burlacu A, Grigorescu G, Rosca AM, Preda MB, Simionescu M. Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells Dev. 2013; 22, 643–653. BurlacuA GrigorescuG RoscaAM PredaMB SimionescuM Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro Stem Cells Dev. 2013 22 643 653 10.1089/scd.2012.0273356446622947186 Search in Google Scholar

7 Zhang M, Mal N, Kiedrowski M, Chacko M, Askari AT, Popovic ZB, Koc ON, Penn MS. SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J. 2007; 21, 3197–3207. ZhangM MalN KiedrowskiM ChackoM AskariAT PopovicZB KocON PennMS SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction FASEB J. 2007 21 3197 3207 10.1096/fj.06-6558com17496162 Search in Google Scholar

8 Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by Mesenchymal Stem Cells. Diabetes 2008; 57, 1759–1767. AbdiR FiorinaP AdraCN AtkinsonM SayeghMH Immunomodulation by Mesenchymal Stem Cells Diabetes 2008 57 1759 1767 10.2337/db08-0180245363118586907 Search in Google Scholar

9 Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. WeissARR DahlkeMH Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs Front Immunol. 2019 10 1191 10.3389/fimmu.2019.01191655797931214172 Search in Google Scholar

10 Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y. Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 2005; 309, 314–317. DezawaM IshikawaH ItokazuY YoshiharaT HoshinoM TakedaS IdeC NabeshimaY Bone marrow stromal cells generate muscle cells and repair muscle degeneration Science 2005 309 314 317 10.1126/science.111036416002622 Search in Google Scholar

11 Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J. Immunol. 2008; 180, 2581–2587. SasakiM AbeR FujitaY AndoS InokumaD ShimizuH Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type J. Immunol. 2008 180 2581 2587 10.4049/jimmunol.180.4.258118250469 Search in Google Scholar

12 Shabbir A, Zisa D, Suzuki G, Lee T. Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen. Am J Physiol Heart Circ Physiol. 2009;296(6):H1888–97. ShabbirA ZisaD SuzukiG LeeT Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen Am J Physiol Heart Circ Physiol 2009 296 6 H1888 97 10.1152/ajpheart.00186.2009271610019395555 Search in Google Scholar

13 Preda MB, Rønningen T, Burlacu A, Simionescu M, Moskaug JØ, Valen G. Remote transplantation of mesenchymal stem cells protects the heart against ischemia-reperfusion injury. Stem Cells. 2014;32(8):2123–2134. PredaMB RønningenT BurlacuA SimionescuM MoskaugJØ ValenG Remote transplantation of mesenchymal stem cells protects the heart against ischemia-reperfusion injury Stem Cells. 2014 32 8 2123 2134 10.1002/stem.168724578312 Search in Google Scholar

14 Preda MB, Lupan A-M, Neculachi CA, Leti LI, Fenyo IM, Popescu S, Rusu EG, Marinescu CI, Simionescu M, Burlacu A. Evidence of mesenchymal stromal cell adaptation to local microenvironment following subcutaneous transplantation. J Cell Mol Med. 2020;24(18):10889–10897. PredaMB LupanA-M NeculachiCA LetiLI FenyoIM PopescuS RusuEG MarinescuCI SimionescuM BurlacuA Evidence of mesenchymal stromal cell adaptation to local microenvironment following subcutaneous transplantation J Cell Mol Med. 2020 24 18 10889 10897 10.1111/jcmm.15717752128532785979 Search in Google Scholar

15 Lee TM, Harn HJ, Chiou TW, Chuang MH, Chen CH, Chuang CH, Lin PC, Lin SZ. Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats. Redox Biol. 2019;27:101170. LeeTM HarnHJ ChiouTW ChuangMH ChenCH ChuangCH LinPC LinSZ Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats Redox Biol. 2019 27 101170 10.1016/j.redox.2019.101170685958331164286 Search in Google Scholar

16 Saeedi P, Halabian R, Imani Fooladi AA. A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies. Stem Cell Investig. 2019;6:34–34. SaeediP HalabianR Imani FooladiAA A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies Stem Cell Investig. 2019 6 34 34 10.21037/sci.2019.08.11678920231620481 Search in Google Scholar

17 Karantalis V, Hare MJ. Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease. Circ Res. 2015;116(8):1413–1430. KarantalisV HareMJ Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease Circ Res. 2015 116 8 1413 1430 10.1161/CIRCRESAHA.116.303614442929425858066 Search in Google Scholar

18 Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, Tse HF, Fu QL, Lian Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(1):e2062. GaoF ChiuSM MotanDA ZhangZ ChenL JiHL TseHF FuQL LianQ Mesenchymal stem cells and immunomodulation: current status and future prospects Cell Death Dis 2016 7 1 e2062 10.1038/cddis.2015.327481616426794657 Search in Google Scholar

19 Cho DI, Kim MR, Jeong H, Jeong HC, Jeong MH, Yoon SH, Kim YS, Ahn Y. Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Exp Mol Med. 2014;46(1). ChoDI KimMR JeongH JeongHC JeongMH YoonSH KimYS AhnY Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages Exp Mol Med 2014 46 1 10.1038/emm.2013.135390988824406319 Search in Google Scholar

20 Li L, Chen X, Wang WE, Zeng C. How to improve the survival of trnasplanted mesenchymal stem cell in inschemic heart? Stem Cells Int. 2016;2016(2):14. LiL ChenX WangWE ZengC How to improve the survival of trnasplanted mesenchymal stem cell in inschemic heart? Stem Cells Int. 2016 2016 2 14 Search in Google Scholar

21 Spencer JA, Ferraro F, Roussakis E, Klein A, Wu J, Runnels JM, Zaher W, Mortensen LJ, Alt C, Turcotte R, Yusuf R, Côté D, Vinogradov SA, Scadden DT, Lin CP. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature. 2014;508(7495):269–273. SpencerJA FerraroF RoussakisE KleinA WuJ RunnelsJM ZaherW MortensenLJ AltC TurcotteR YusufR CôtéD VinogradovSA ScaddenDT LinCP Direct measurement of local oxygen concentration in the bone marrow of live animals Nature. 2014 508 7495 269 273 10.1038/nature13034398435324590072 Search in Google Scholar

22 Mann DL. Stress-Activated Cytokines and The Heart: From Adaptation to Maladaptation. Annu Rev Physiol. 2003;65:81–101. MannDL Stress-Activated Cytokines and The Heart: From Adaptation to Maladaptation Annu Rev Physiol. 2003 65 81 101 10.1146/annurev.physiol.65.092101.14224912500970 Search in Google Scholar

23 Yin JQ, Zhu J, Ankrum JA. Manufacturing of primed mesenchymal stromal cells for therapy. Nat Biomed Eng. 2019;3(2):90–104. YinJQ ZhuJ AnkrumJA Manufacturing of primed mesenchymal stromal cells for therapy Nat Biomed Eng. 2019 3 2 90 104 10.1038/s41551-018-0325-830944433 Search in Google Scholar

24 Li W, Ren G, Huang Y, Han Y, Li J, Chen X, Cao K, Chen Q, Shou P, Zhang L, Yuan ZR, Roberts AI, Shi S, Le AD, Shi Y. Mesenchymal stem cells: a double-edged sword in regulating immune responses. Cell Death Differ. 2012;19:1505–1513. LiW RenG HuangY HanY LiJ ChenX CaoK ChenQ ShouP ZhangL YuanZR RobertsAI ShiS LeAD ShiY Mesenchymal stem cells: a double-edged sword in regulating immune responses Cell Death Differ. 2012 19 1505 1513 10.1038/cdd.2012.26342247322421969 Search in Google Scholar

25 Song N, Scholtemeijer M, Shah K. Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends Pharmacol Sci. 2020;41(9):653–664. SongN ScholtemeijerM ShahK Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential Trends Pharmacol Sci. 2020 41 9 653 664 10.1016/j.tips.2020.06.009775184432709406 Search in Google Scholar

26 Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. 2008;111(3):1327–1333. SpaggiariGM CapobiancoA AbdelrazikH BecchettiF MingariMC MorettaL Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2 Blood. 2008 111 3 1327 1333 10.1182/blood-2007-02-07499717951526 Search in Google Scholar

27 Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal Stem Cell-Mediated Immunosuppression Occurs via Concerted Action of Chemokines and Nitric Oxide. Cell Stem Cell. 2008;2(2):141–150. RenG ZhangL ZhaoX XuG ZhangY RobertsAI ZhaoRC ShiY Mesenchymal Stem Cell-Mediated Immunosuppression Occurs via Concerted Action of Chemokines and Nitric Oxide Cell Stem Cell. 2008 2 2 141 150 10.1016/j.stem.2007.11.01418371435 Search in Google Scholar

28 Preda MB, Rosca AM, Tutuianu R, Burlacu A. Pre-stimulation with FGF-2 increases in vitro functional coupling of mesenchymal stem cells with cardiac cells. Biochem Biophys Res Commun. 2015;464(2):667–673. PredaMB RoscaAM TutuianuR BurlacuA Pre-stimulation with FGF-2 increases in vitro functional coupling of mesenchymal stem cells with cardiac cells Biochem Biophys Res Commun. 2015 464 2 667 673 10.1016/j.bbrc.2015.07.05526187662 Search in Google Scholar

29 Bryan NS, Grisham MB. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med. 2007;43(5):645–657. BryanNS GrishamMB Methods to detect nitric oxide and its metabolites in biological samples Free Radic Biol Med. 2007 43 5 645 657 10.1016/j.freeradbiomed.2007.04.026204191917664129 Search in Google Scholar

30 Preda MB, Neculachi CA, Fenyo IM, Vacaru AM, Publik MA, Simionescu M, Burlacu A. Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice. Cell Death & Disease 2021; 12, 566. PredaMB NeculachiCA FenyoIM VacaruAM PublikMA SimionescuM BurlacuA Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice Cell Death & Disease 2021 12 566 10.1038/s41419-021-03839-w816968234075029 Search in Google Scholar

31 Caplan H, Olson SD, Kumar A, George M, Prabhakara KS, Wenzel P, Bedi S, Toledano-Furman NE, Triolo F, Kamhieh-Milz J, Moll G, Cox CS Jr. Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges to Clinical Application. Front Immunol. 2019;10(July):1645. CaplanH OlsonSD KumarA GeorgeM PrabhakaraKS WenzelP BediS Toledano-FurmanNE TrioloF Kamhieh-MilzJ MollG CoxCSJr Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges to Clinical Application Front Immunol 2019 10 July 1645 10.3389/fimmu.2019.01645668505931417542 Search in Google Scholar

32 Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010;12:87–117. ParekkadanB MilwidJM Mesenchymal stem cells as therapeutics Annu Rev Biomed Eng. 2010 12 87 117 10.1146/annurev-bioeng-070909-105309375951920415588 Search in Google Scholar

33 Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat Biotechnol. 2014;32(3):252–260. AnkrumJA OngJF KarpJM Mesenchymal stem cells: Immune evasive, not immune privileged Nat Biotechnol. 2014 32 3 252 260 10.1038/nbt.2816432064724561556 Search in Google Scholar

34 Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, Wang CY. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013; 19(1):35–42. BiancoP CaoX FrenettePS MaoJJ RobeyPG SimmonsPJ WangCY The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine Nat Med. 2013 19 1 35 42 10.1038/nm.3028399810323296015 Search in Google Scholar

35 Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007;109(1):228–34. SatoK OzakiK OhI MeguroA HatanakaK NagaiT MuroiK OzawaK Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells Blood 2007 109 1 228 34 10.1182/blood-2006-02-00224616985180 Search in Google Scholar

36 Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Cell Death Differ. 2014;21(2):216–25. MaS XieN LiW YuanB ShiY WangY Immunobiology of mesenchymal stem cells Cell Death Differ. 2014 21 2 216 25 10.1038/cdd.2013.158389095524185619 Search in Google Scholar

37 Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W, Wang S, Shi S. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nature Medicine 2011;17(12):1594–601. LiuY WangL KikuiriT AkiyamaK ChenC XuX YangR ChenW WangS ShiS Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α Nature Medicine 2011 17 12 1594 601 10.1038/nm.2542323365022101767 Search in Google Scholar

38 Hu A, Liu HB, Mlynski R, Plontke S, Zhang JF, Dai WJ, Duan JL, Fan JP, Zheng HL, Xu WH, Chen XP, Huang JJ. Therapeutic ultrasound potentiates the anti-nociceptive and anti-inflammatory effects of curcumin to postoperative pain via Sirt1/NF-κB signaling pathway. American Journal of Translational Research. 2018;10:3099–3110. HuA LiuHB MlynskiR PlontkeS ZhangJF DaiWJ DuanJL FanJP ZhengHL XuWH ChenXP HuangJJ Therapeutic ultrasound potentiates the anti-nociceptive and anti-inflammatory effects of curcumin to postoperative pain via Sirt1/NF-κB signaling pathway American Journal of Translational Research. 2018 10 3099 3110 Search in Google Scholar

39 Giri J, Galipeau J. Mesenchymal stromal cell therapeutic potency is dependent upon viability, route of delivery, and immune match. Blood Adv. 2020;4(9):1987–1997. GiriJ GalipeauJ Mesenchymal stromal cell therapeutic potency is dependent upon viability, route of delivery, and immune match Blood Adv. 2020 4 9 1987 1997 10.1182/bloodadvances.2020001711721843532384543 Search in Google Scholar

40 Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, von Bonin M, Barbieri L, Halai K, Ward S, Weng L, Chakraverty R, Lombardi G, Watt FM, Orchard K, Marks DI, Apperley J, Bornhauser M, Walczak H, Bennett C, Dazzi F. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med. 2017; 9(416). GalleuA Riffo-VasquezY TrentoC LomasC DolcettiL CheungTS von BoninM BarbieriL HalaiK WardS WengL ChakravertyR LombardiG WattFM OrchardK MarksDI ApperleyJ BornhauserM WalczakH BennettC DazziF Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation Sci Transl Med. 2017 9 416 10.1126/scitranslmed.aam782829141887 Search in Google Scholar

41 Vagnozzi RJ, Maillet M, Sargent MA, Khalil H, Johansen AKZ, Schwanekamp JA, York AJ, Huang V, Nahrendorf M, Sadayappan S, Molkentin JD. An acute immune response underlies the benefit of cardiac stem cell therapy. Nature. 2020;577(7790):405–409. VagnozziRJ MailletM SargentMA KhalilH JohansenAKZ SchwanekampJA YorkAJ HuangV NahrendorfM SadayappanS MolkentinJD An acute immune response underlies the benefit of cardiac stem cell therapy Nature. 2020 577 7790 405 409 10.1038/s41586-019-1802-2696257031775156 Search in Google Scholar

42 Keeley TP, Mann GE. Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans. Physiol Rev. 2019;99(1):161–234. KeeleyTP MannGE Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans Physiol Rev. 2019 99 1 161 234 10.1152/physrev.00041.201730354965 Search in Google Scholar

43 Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hipoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells. Stem Cells. 2008;26(8):2173–2182. RosovaI DaoM CapocciaB LinkD NoltaJA Hipoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells Stem Cells. 2008 26 8 2173 2182 10.1634/stemcells.2007-1104301747718511601 Search in Google Scholar

44 Mas-Bargues C, Sanz-Ros J, Román-Domínguez A, Inglés M, Gimeno-Mallench L, El Alami M, Viña-Almunia J, Gambini J, Viña J, Borrás C. Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine. Int J Mol Sci. 2019; 20(5):1195. Mas-BarguesC Sanz-RosJ Román-DomínguezA InglésM Gimeno-MallenchL El AlamiM Viña-AlmuniaJ GambiniJ ViñaJ BorrásC Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine Int J Mol Sci. 2019 20 5 1195 10.3390/ijms20051195642952230857245 Search in Google Scholar