Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials

Li-Tzu Wang, Chiao-Hsuan Ting, Men-Luh Yen, Ko-Jiunn Liu, Huey-Kang Sytwu, Kenneth K Wu, B Linju Yen, Li-Tzu Wang, Chiao-Hsuan Ting, Men-Luh Yen, Ko-Jiunn Liu, Huey-Kang Sytwu, Kenneth K Wu, B Linju Yen

Abstract

Human mesenchymal stem cells (MSCs) are multilineage somatic progenitor/stem cells that have been shown to possess immunomodulatory properties in recent years. Initially met with much skepticism, MSC immunomodulation has now been well reproduced across tissue sources and species to be clinically relevant. This has opened up the use of these versatile cells for application as 3rd party/allogeneic use in cell replacement/tissue regeneration, as well as for immune- and inflammation-mediated disease entities. Most surprisingly, use of MSCs for in immune-/inflammation-mediated diseases appears to yield more efficacy than for regenerative medicine, since engraftment of the exogenous cell does not appear necessary. In this review, we focus on this non-traditional clinical use of a tissue-specific stem cell, and highlight important findings and trends in this exciting area of stem cell therapy.

Keywords: Autoimmune disease; Clinical trials; Human; Immunomodulation; Inflammation; Mesenchymal stem cells; Organ transplantation and rejection; Stem cell therapy.

Figures

Fig. 1
Fig. 1
Clinical application of human mesenchymal stem cells (MSCs) for immune- and inflammation-mediated diseases. Graph is a summary of the number of clinical trials using MSC therapy in immune-/inflammation-mediated diseases, as registered on the website https://clinicaltrials.gov/ (accessed April 2016). MS, multiple sclerosis; T1DM, type 1 diabetes mellitus; GVHD, graft versus host disease; OA, osteoarthritis; IBD, inflammatory bowel disease
Fig. 2
Fig. 2
MSC-derived paracrine factors mediate immunomodulatory functions, particularly towards T lymphocytes, in preclinical animal studies of various immune-and inflammation-mediated diseases
Fig. 3
Fig. 3
Mechanisms involved in MSC therapy for inflammatory pulmonary diseases based on preclinical animal studies. Immunomodulatory effects include enhancing bacterial clearance by direct killing and enhancement of macrophage phagocytosis; decreasing inflammatory response by modulation of macrophages towards an M2 phenotype and inhibition of neutrophil recruitment; as well as reducing damage to alveolar epithelium

References

    1. Hochedlinger K, Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med. 2003;349(3):275–286. doi: 10.1056/NEJMra035397.
    1. Korbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med. 2003;349(6):570–582. doi: 10.1056/NEJMra022361.
    1. Boo M, Van Walraven SM, Chapman J, Lindberg B, Schmidt AH, Shaw BE, Switzer GE, Yang E, Egeland T. Remuneration of hematopoietic stem cell donors: principles and perspective of the World Marrow Donor Association. Blood. 2011;117(1):21–25. doi: 10.1182/blood-2010-07-298430.
    1. Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med. 2006;355(12):1274–1277. doi: 10.1056/NEJMe068172.
    1. Von Bahr L, Batsis I, Moll G, Hagg 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. doi: 10.1002/stem.1118.
    1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147. doi: 10.1126/science.284.5411.143.
    1. Friedenstein AJ. Precursor cells of mechanocytes. Int Rev Cytol. 1976;47:327–359. doi: 10.1016/S0074-7696(08)60092-3.
    1. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307–316.
    1. Hass R, Kasper C, Bohm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9:12. doi: 10.1186/1478-811X-9-12.
    1. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther position statement Cytotherapy. 2006;8(4):315–317.
    1. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42–48. doi: 10.1016/S0301-472X(01)00769-X.
    1. Di Nicola M, 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. doi: 10.1182/blood.V99.10.3838.
    1. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden 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. doi: 10.1046/j.1365-3083.2003.01176.x.
    1. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363(9419):1439–1441. doi: 10.1016/S0140-6736(04)16104-7.
    1. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110(10):3499–3506. doi: 10.1182/blood-2007-02-069716.
    1. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726–736. doi: 10.1038/nri2395.
    1. Gotherstrom C, Ringden O, Tammik C, Zetterberg E, Westgren M, Le Blanc K. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol. 2004;190(1):239–245. doi: 10.1016/j.ajog.2003.07.022.
    1. Chang CJ, Yen ML, Chen YC, Chien CC, Huang HI, Bai CH, Yen BL. Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells. 2006;24(11):2466–2477. doi: 10.1634/stemcells.2006-0071.
    1. Griffin MD, Elliman SJ, Cahill E, English K, Ceredig R, Ritter T. Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots? Stem Cells. 2013;31(10):2033–2041. doi: 10.1002/stem.1452.
    1. Tyndall A. Mesenchymal stem cell treatments in rheumatology: a glass half full? Nat Rev Rheumatol. 2014;10(2):117–124. doi: 10.1038/nrrheum.2013.166.
    1. Wang L, Zhao Y, Shi S. Interplay between mesenchymal stem cells and lymphocytes: implications for immunotherapy and tissue regeneration. J Dent Res. 2012;91(11):1003–1010. doi: 10.1177/0022034512460404.
    1. Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011;2(4):34. doi: 10.1186/scrt75.
    1. Engela AU, Baan CC, Litjens NH, Franquesa M, Betjes MG, Weimar W, Hoogduijn MJ. Mesenchymal stem cells control alloreactive CD8(+) CD28(−) T cells. Clin Exp Immunol. 2013;174(3):449–458. doi: 10.1111/cei.12199.
    1. Li M, Sun X, Kuang X, Liao Y, Li H, Luo D. Mesenchymal stem cells suppress CD8+ T cell-mediated activation by suppressing natural killer group 2, member D protein receptor expression and secretion of prostaglandin E2, indoleamine 2, 3-dioxygenase and transforming growth factor-beta. Clin Exp Immunol. 2014;178(3):516–524. doi: 10.1111/cei.12423.
    1. Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci. 2011;18:49. doi: 10.1186/1423-0127-18-49.
    1. Augello A, Tasso R, Negrini SM, Amateis A, Indiveri F, Cancedda R, Pennesi G. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol. 2005;35(5):1482–1490. doi: 10.1002/eji.200425405.
    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. Blood. 2006;107(1):367–372. doi: 10.1182/blood-2005-07-2657.
    1. Chen PM, Liu KJ, Hsu PJ, Wei CF, Bai CH, Ho LJ, Sytwu HK, Yen BL. Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2. J Leukoc Biol. 2014;96(2):295–303. doi: 10.1189/jlb.3A0513-242R.
    1. Cutler AJ, Limbani V, Girdlestone J, Navarrete CV. Umbilical cord-derived mesenchymal stromal cells modulate monocyte function to suppress T cell proliferation. J Immunol. 2010;185(11):6617–6623. doi: 10.4049/jimmunol.1002239.
    1. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120–4126. doi: 10.1182/blood-2004-02-0586.
    1. Chiesa S, Morbelli S, Morando S, Massollo M, Marini C, Bertoni A, Frassoni F, Bartolome ST, Sambuceti G, Traggiai E, Uccelli A. Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proc Natl Acad Sci U S A. 2011;108(42):17384–17389. doi: 10.1073/pnas.1103650108.
    1. Nemeth K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–49. doi: 10.1038/nm.1905.
    1. Oh JY, Ko JH, Lee HJ, Yu JM, Choi H, Kim MK, Wee WR, Prockop DJ. Mesenchymal stem/stromal cells inhibit the NLRP3 inflammasome by decreasing mitochondrial reactive oxygen species. Stem Cells. 2014;32(6):1553–1563. doi: 10.1002/stem.1608.
    1. Yen BL, Yen ML, Hsu PJ, Liu KJ, Wang CJ, Bai CH, Sytwu HK. Multipotent human mesenchymal stromal cells mediate expansion of myeloid-derived suppressor cells via hepatocyte growth factor/c-met and STAT3. Stem Cell Reports. 2013;1(2):139–151. doi: 10.1016/j.stemcr.2013.06.006.
    1. Chen CP, Chen YY, Huang JP, Wu YH. The effect of conditioned medium derived from human placental multipotent mesenchymal stromal cells on neutrophils: possible implications for placental infection. Mol Hum Reprod. 2014;20(11):1117–1125. doi: 10.1093/molehr/gau062.
    1. Cassatella MA, Mosna F, Micheletti A, Lisi V, Tamassia N, Cont C, Calzetti F, Pelletier M, Pizzolo G, Krampera M. Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells. 2011;29(6):1001–1011. doi: 10.1002/stem.651.
    1. Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol. 2011;10(7):649–656. doi: 10.1016/S1474-4422(11)70121-1.
    1. Connick P, Kolappan M, Patani R, Scott MA, Crawley C, He XL, Richardson K, Barber K, Webber DJ, Wheeler-Kingshott CA, Tozer DJ, Samson RS, Thomas DL, Du MQ, Luan SL, Michell AW, Altmann DR, Thompson AJ, Miller DH, Compston A, Chandran S. The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments. Trials. 2011;12:62. doi: 10.1186/1745-6215-12-62.
    1. Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010;16(6):838–847. doi: 10.1016/j.bbmt.2010.01.011.
    1. Introna M, Lucchini G, Dander E, Galimberti S, Rovelli A, Balduzzi A, Longoni D, Pavan F, Masciocchi F, Algarotti A, Mico C, Grassi A, Deola S, Cavattoni I, Gaipa G, Belotti D, Perseghin P, Parma M, Pogliani E, Golay J, Pedrini O, Capelli C, Cortelazzo S, D’Amico G, Biondi A, Rambaldi A, Biagi E. Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant. 2014;20(3):375–381. doi: 10.1016/j.bbmt.2013.11.033.
    1. Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez CM, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011;96(7):1072–1076. doi: 10.3324/haematol.2010.038356.
    1. Emadedin M, Ghorbani LM, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, Hosseini SE, Niknejadi M, Moeininia F, Aghahossein FA, Baghban ER, Vosough DA, Labibzadeh N, Mirazimi BA, Baharvand H, Aghdami N. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015;18(6):336–344.
    1. Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014;32(5):1254–1266. doi: 10.1002/stem.1634.
    1. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: 2-year follow-up results. Transplantation. 2014;97(11):e66–e68. doi: 10.1097/TP.0000000000000167.
    1. Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015;99(8):1681–1690. doi: 10.1097/TP.0000000000000678.
    1. Vives J, Oliver-Vila I, Pla A. Quality compliance in the shift from cell transplantation to cell therapy in non-pharma environments. Cytotherapy. 2015;17(8):1009–1014. doi: 10.1016/j.jcyt.2015.02.002.
    1. Forbes GM, Sturm MJ, Leong RW, Sparrow MP, Segarajasingam D, Cummins AG, Phillips M, Herrmann RP. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy. Clin Gastroenterol Hepatol. 2014;12(1):64–71. doi: 10.1016/j.cgh.2013.06.021.
    1. Molendijk I, Bonsing BA, Roelofs H, Peeters KC, Wasser MN, Dijkstra G, van der Woude CJ, Duijvestein M, Veenendaal RA, Zwaginga JJ, Verspaget HW, Fibbe WE, van der Meulen-de Jong AE, Hommes DW. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn’s Disease. Gastroenterology. 2015;149(4):918–927 e916. doi: 10.1053/j.gastro.2015.06.014.
    1. Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014;164(5):966–972 e966. doi: 10.1016/j.jpeds.2013.12.011.
    1. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013;143(6):1590–1598. doi: 10.1378/chest.12-2094.
    1. Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015;3(1):24–32. doi: 10.1016/S2213-2600(14)70291-7.
    1. Quesenberry P, Levitt L. Hematopoietic stem cells. N Engl J Med. 1979;301(14):755–761. doi: 10.1056/NEJM197910043011404.
    1. Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015;125(4):606–615. doi: 10.1182/blood-2014-08-551994.
    1. Levine JE, Paczesny S, Sarantopoulos S. Clinical applications for biomarkers of acute and chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(1 Suppl):S116–S124. doi: 10.1016/j.bbmt.2011.10.019.
    1. Szyska M, Na IK. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016;7:118. doi: 10.3389/fimmu.2016.00118.
    1. Kurtzberg J, Prockop S, Teira P, Bittencourt H, Lewis V, Chan KW, Horn B, Yu L, Talano JA, Nemecek E, Mills CR, Chaudhury S. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant. 2014;20(2):229–235. doi: 10.1016/j.bbmt.2013.11.001.
    1. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371(9624):1579–1586. doi: 10.1016/S0140-6736(08)60690-X.
    1. Sanchez-Guijo FM, Lopez-Villar O, Lopez-Anglada L, Villaron EM, Muntion S, Diez-Campelo M, Perez-Simon JA, San Miguel JF, Caballero D, Del Canizo MC. Allogeneic mesenchymal stem cell therapy for refractory cytopenias after hematopoietic stem cell transplantation. Transfusion. 2012;52(5):1086–1091. doi: 10.1111/j.1537-2995.2011.03400.x.
    1. Weng J, He C, Lai P, Luo C, Guo R, Wu S, Geng S, Xiangpeng A, Liu X, Du X. Mesenchymal stromal cells treatment attenuates dry eye in patients with chronic graft-versus-host disease. Mol Ther. 2012;20(12):2347–2354. doi: 10.1038/mt.2012.208.
    1. Weng JY, Du X, Geng SX, Peng YW, Wang Z, Lu ZS, Wu SJ, Luo CW, Guo R, Ling W, Deng CX, Liao PJ, Xiang AP. Mesenchymal stem cell as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant. 2010;45(12):1732–1740. doi: 10.1038/bmt.2010.195.
    1. Baker M. Stem cells: Fast and furious. Nature. 2009;458(7241):962–965. doi: 10.1038/458962a.
    1. Rizk M, Monaghan M, Shorr R, Kekre N, Bredeson CN, Allan DS. Heterogeneity in studies of mesenchymal stromal cells to treat or prevent GVHD: a scoping review of the evidence. Biol Blood Marrow Transplant. 2016;22(8):1416–1423. doi: 10.1016/j.bbmt.2016.04.010.
    1. Galipeau J. The mesenchymal stromal cells dilemma--does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 2013;15(1):2–8. doi: 10.1016/j.jcyt.2012.10.002.
    1. Moll G, Alm JJ, Davies LC, Von Bahr L, Heldring N, Stenbeck-Funke L, Hamad OA, Hinsch R, Ignatowicz L, Locke M, Lonnies H, Lambris JD, Teramura Y, Nilsson-Ekdahl K, Nilsson B, Le Blanc K. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells. 2014;32(9):2430–2442. doi: 10.1002/stem.1729.
    1. Coghill JM, Sarantopoulos S, Moran TP, Murphy WJ, Blazar BR, Serody JS. Effector CD4+ T cells, the cytokines they generate, and GVHD: something old and something new. Blood. 2011;117(12):3268–3276. doi: 10.1182/blood-2010-12-290403.
    1. Li H, Guo Z, Jiang X, Zhu H, Li X, Mao N. Mesenchymal stem cells alter migratory property of T and dendritic cells to delay the development of murine lethal acute graft-versus-host disease. Stem Cells. 2008;26(10):2531–2541. doi: 10.1634/stemcells.2008-0146.
    1. Robles JD, Liu YP, Cao J, Xiang Z, Cai Y, Manio M, Tang EH, Chan GC. Immunosuppressive mechanisms of human bone marrow derived mesenchymal stromal cells in BALB/c host graft versus host disease murine models. Exp Hematol Oncol. 2015;4:13. doi: 10.1186/s40164-015-0007-0.
    1. Tobin LM, Healy ME, English K, Mahon BP. Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease. Clin Exp Immunol. 2013;172(2):333–348. doi: 10.1111/cei.12056.
    1. Auletta JJ, Eid SK, Wuttisarnwattana P, Silva I, Metheny L, Keller MD, Guardia-Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga LA, Ganguly S, Tyler M, Wilson DL, Cooke KR. Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation. Stem Cells. 2015;33(2):601–614. doi: 10.1002/stem.1867.
    1. 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. doi: 10.1016/j.stem.2007.11.014.
    1. Gregoire-Gauthier J, Selleri S, Fontaine F, Dieng MM, Patey N, Despars G, Beausejour CM, Haddad E. Therapeutic efficacy of cord blood-derived mesenchymal stromal cells for the prevention of acute graft-versus-host disease in a xenogenic mouse model. Stem Cells Dev. 2012;21(10):1616–1626. doi: 10.1089/scd.2011.0413.
    1. Jang MJ, Kim HS, Lee HG, Kim GJ, Jeon HG, Shin HS, Chang SK, Hur GH, Chong SY, Oh D, Chung HM. Placenta-derived mesenchymal stem cells have an immunomodulatory effect that can control acute graft-versus-host disease in mice. Acta Haematol. 2013;129(4):197–206. doi: 10.1159/000345267.
    1. Jang YK, Kim M, Lee YH, Oh W, Yang YS, Choi SJ. Optimization of the therapeutic efficacy of human umbilical cord blood-mesenchymal stromal cells in an NSG mouse xenograft model of graft-versus-host disease. Cytotherapy. 2014;16(3):298–308. doi: 10.1016/j.jcyt.2013.10.012.
    1. Luz-Crawford P, Torres MJ, Noel D, Fernandez A, Toupet K, Alcayaga-Miranda F, Tejedor G, Jorgensen C, Illanes SE, Figueroa FE, Djouad F, Khoury M. The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases. Stem Cells. 2016;34(2):456–469. doi: 10.1002/stem.2244.
    1. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S, Frassoni F, Locatelli F. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica. 2005;90(4):516–525.
    1. Verneris MR. Natural killer cells and regulatory T cells: how to manipulate a graft for optimal GVL. Hematology Am Soc Hematol Educ Program. 2013;2013:335–341.
    1. Hedegaard CJ, Krakauer M, Bendtzen K, Lund H, Sellebjerg F, Nielsen CH. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology. 2008;125(2):161–169. doi: 10.1111/j.1365-2567.2008.02837.x.
    1. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A. Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nat Med. 2007;13(10):1173–1175. doi: 10.1038/nm1651.
    1. Carnegie PR. Amino acid sequence of the encephalitogenic basic protein from human myelin. Biochem J. 1971;123(1):57–67. doi: 10.1042/bj1230057.
    1. Feinstein A, Freeman J, Lo AC. Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Lancet Neurol. 2015;14(2):194–207. doi: 10.1016/S1474-4422(14)70231-5.
    1. Global Burden of Disease Study 2013 Collaborators Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743–800. doi: 10.1016/S0140-6736(15)60692-4.
    1. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106(5):1755–1761. doi: 10.1182/blood-2005-04-1496.
    1. Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009;57(11):1192–1203. doi: 10.1002/glia.20841.
    1. Lanz TV, Opitz CA, Ho PP, Agrawal A, Lutz C, Weller M, Mellor AL, Steinman L, Wick W, Platten M. Mouse mesenchymal stem cells suppress antigen-specific TH cell immunity independent of indoleamine 2,3-dioxygenase 1 (IDO1) Stem Cells Dev. 2010;19(5):657–668. doi: 10.1089/scd.2009.0385.
    1. Sajic M, Hunt DP, Lee W, Compston DA, Schweimer JV, Gregson NA, Chandran S, Smith KJ. Mesenchymal stem cells lack efficacy in the treatment of experimental autoimmune neuritis despite in vitro inhibition of T-cell proliferation. PLoS One. 2012;7(2) doi: 10.1371/journal.pone.0030708.
    1. Luz-Crawford P, Kurte M, Bravo-Alegria J, Contreras R, Nova-Lamperti E, Tejedor G, Noel D, Jorgensen C, Figueroa F, Djouad F, Carrion F. Mesenchymal stem cells generate a CD4 + CD25 + Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther. 2013;4(3):65. doi: 10.1186/scrt216.
    1. Rafei M, Campeau PM, Aguilar-Mahecha A, Buchanan M, Williams P, Birman E, Yuan S, Young YK, Boivin MN, Forner K, Basik M, Galipeau J. Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. J Immunol. 2009;182(10):5994–6002. doi: 10.4049/jimmunol.0803962.
    1. Ben-Ami E, Miller A, Berrih-Aknin S. T cells from autoimmune patients display reduced sensitivity to immunoregulation by mesenchymal stem cells: role of IL-2. Autoimmun Rev. 2014;13(2):187–196. doi: 10.1016/j.autrev.2013.09.007.
    1. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64(9):1263–1267. doi: 10.1136/ard.2004.025270.
    1. Noth U, Steinert AF, Tuan RS. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nature clinical practice. Rheumatology. 2008;4(7):371–380.
    1. Horie M, Choi H, Lee RH, Reger RL, Ylostalo J, Muneta T, Sekiya I, Prockop DJ. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis Cartilage. 2012;20(10):1197–1207. doi: 10.1016/j.joca.2012.06.002.
    1. Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14(1):R31. doi: 10.1186/ar3735.
    1. Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi NS, Nazhvani DS, Ghaderi A. Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med. 2012;15(8):495–499.
    1. Soler R, Orozco L, Munar A, Huguet M, Lopez R, Vives J, Coll R, Codinach M, Garcia-Lopez J. Final results of a phase I-II trial using ex vivo expanded autologous Mesenchymal Stromal Cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee. 2016;23(4):647–654. doi: 10.1016/j.knee.2015.08.013.
    1. Seki N, Sudo Y, Mizuhara H, Orito K, Imasaki A, Ono S, Hamaoka T, Senoh H, Fujiwara H. Type II collagen-induced murine arthritis: induction of arthritis depends on antigen-presenting cell function as well as susceptibility of host to an anticollagen immune response. J Immunol. 1992;148(10):3093–3099.
    1. Bouffi C, Djouad F, Mathieu M, Noel D, Jorgensen C. Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? Rheumatology (Oxford) 2009;48(10):1185–1189. doi: 10.1093/rheumatology/kep162.
    1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066–2078. doi: 10.1056/NEJMra0804647.
    1. Chinnadurai R, Ng S, Velu V, Galipeau J. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. World J Gastroenterol. 2015;21(16):4779–4787. doi: 10.3748/wjg.v21.i16.4779.
    1. Abdel Salam AG, Ata HM, Salman TM, Rashed LA, Sabry D, Schaalan MF. Potential therapeutic utility of mesenchymal stem cells in inflammatory bowel disease in mice. Int Immunopharmacol. 2014;22(2):515–521. doi: 10.1016/j.intimp.2014.07.030.
    1. He XW, He XS, Lian L, Wu XJ, Lan P. Systemic infusion of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis in mice. Dig Dis Sci. 2012;57(12):3136–3144. doi: 10.1007/s10620-012-2290-5.
    1. Forte D, Ciciarello M, Valerii MC, De Fazio L, Cavazza E, Giordano R, Parazzi V, Lazzari L, Laureti S, Rizzello F, Cavo M, Curti A, Lemoli RM, Spisni E, Catani L. Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn’s disease patients in a mouse model of colitis. Stem Cell Res Ther. 2015;6:170. doi: 10.1186/s13287-015-0166-2.
    1. Sala E, Genua M, Petti L, Anselmo A, Arena V, Cibella J, Zanotti L, D’Alessio S, Scaldaferri F, Luca G, Arato I, Calafiore R, Sgambato A, Rutella S, Locati M, Danese S, Vetrano S. Mesenchymal Stem Cells Reduce Colitis in Mice via Release of TSG6, Independently of Their Localization to the Intestine. Gastroenterology. 2015;149(1):163–176 e120. doi: 10.1053/j.gastro.2015.03.013.
    1. Zuo D, Tang Q, Fan H, Shou Z, Liu X, Cao D, Zou Z. Modulation of nuclear factor-kappaB-mediated pro-inflammatory response is associated with exogenous administration of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis. Mol Med Rep. 2015;11(4):2741–2748.
    1. Ko IK, Kim BG, Awadallah A, Mikulan J, Lin P, Letterio JJ, Dennis JE. Targeting improves MSC treatment of inflammatory bowel disease. Mol Ther. 2010;18(7):1365–1372. doi: 10.1038/mt.2010.54.
    1. Kim DJ, Kim KS, Song MY, Seo SH, Kim SJ, Yang BG, Jang MH, Sung YC. Delivery of IL-12p40 ameliorates DSS-induced colitis by suppressing IL-17A expression and inflammation in the intestinal mucosa. Clin Immunol. 2012;144(3):190–199. doi: 10.1016/j.clim.2012.06.009.
    1. Wang WQ, Dong K, Zhou L, Jiao GH, Zhu CZ, Li WW, Yu G, Wu WT, Chen S, Sun ZN, Wang YM, Liu WT, Zhang J, Wang BM, Feng XM. IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice. Acta Pharmacol Sin. 2015;36(11):1377–1387. doi: 10.1038/aps.2015.51.
    1. Garcia-Olmo D, Schwartz DA. Cumulative Evidence That Mesenchymal Stem Cells Promote Healing of Perianal Fistulas of Patients With Crohn’s Disease--Going From Bench to Bedside. Gastroenterology. 2015;149(4):853–857. doi: 10.1053/j.gastro.2015.08.038.
    1. Melmed GY, Pandak WM, Casey K, Abraham B, Valentine J, Schwartz D, Awais D, Bassan I, Lichtiger S, Sands B, Hanauer S, Richards R, Oikonomou I, Parekh N, Targan S, Johnson K, Hariri R, Fischkoff S. Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohn's Disease: A Phase 1b/2a Study. Inflamm Bowel Dis. 2015;21(8):1809–1816. doi: 10.1097/MIB.0000000000000441.
    1. Inamdar AC, Inamdar AA. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell. Exp Lung Res. 2013;39(8):315–327. doi: 10.3109/01902148.2013.816803.
    1. Walter J, Ware LB, Matthay MA. Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis. Lancet Respir Med. 2014;2(12):1016–1026. doi: 10.1016/S2213-2600(14)70217-6.
    1. Anjos-Afonso F, Siapati EK, Bonnet D. In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J Cell Sci. 2004;117(Pt 23):5655–5664. doi: 10.1242/jcs.01488.
    1. Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003;100(14):8407–8411. doi: 10.1073/pnas.1432929100.
    1. Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng. 2010;12:87–117. doi: 10.1146/annurev-bioeng-070909-105309.
    1. Sinclair K, Yerkovich ST, Chambers DC. Mesenchymal stem cells and the lung. Respirology. 2013;18(3):397–411. doi: 10.1111/resp.12050.
    1. Barnes PJ. Mediators of chronic obstructive pulmonary disease. Pharmacol Rev. 2004;56(4):515–548. doi: 10.1124/pr.56.4.2.
    1. Vlahos R, Bozinovski S. Role of alveolar macrophages in chronic obstructive pulmonary disease. Front Immunol. 2014;5:435. doi: 10.3389/fimmu.2014.00435.
    1. Postma DS, Rabe KF. The Asthma-COPD Overlap Syndrome. N Engl J Med. 2015;373(13):1241–1249. doi: 10.1056/NEJMra1411863.
    1. Kim YS, Kim JY, Huh JW, Lee SW, Choi SJ, Oh YM. The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema. Tuberc Respir Dis (Seoul) 2015;78(3):239–245. doi: 10.4046/trd.2015.78.3.239.
    1. Tibboel J, Keijzer R, Reiss I, De Jongste JC, Post M. Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model of pulmonary emphysema. COPD. 2014;11(3):310–318.
    1. Broekman W, Amatngalim GD, De Mooij-Eijk Y, Oostendorp J, Roelofs H, Taube C, Stolk J, Hiemstra PS. TNF-alpha and IL-1beta-activated human mesenchymal stromal cells increase airway epithelial wound healing in vitro via activation of the epidermal growth factor receptor. Respir Res. 2016;17(1):3. doi: 10.1186/s12931-015-0316-1.
    1. Katsha AM, Ohkouchi S, Xin H, Kanehira M, Sun R, Nukiwa T, Saijo Y. Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol Ther. 2011;19(1):196–203. doi: 10.1038/mt.2010.192.
    1. Guan XJ, Song L, Han FF, Cui ZL, Chen X, Guo XJ, Xu WG. Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors. J Cell Biochem. 2013;114(2):323–335. doi: 10.1002/jcb.24377.
    1. Gu W, Song L, Li XM, Wang D, Guo XJ, Xu WG. Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways. Sci Rep. 2015;5:8733. doi: 10.1038/srep08733.
    1. Gao P, Zhou Y, Xian L, Li C, Xu T, Plunkett B, Huang SK, Wan M, Cao X. Functional effects of TGF-beta1 on mesenchymal stem cell mobilization in cockroach allergen-induced asthma. J Immunol. 2014;192(10):4560–4570. doi: 10.4049/jimmunol.1303461.
    1. Lee SH, Jang AS, Kwon JH, Park SK, Won JH, Park CS. Mesenchymal stem cell transfer suppresses airway remodeling in a toluene diisocyanate-induced murine asthma model. Allergy, Asthma Immunol Res. 2011;3(3):205–211. doi: 10.4168/aair.2011.3.3.205.
    1. Ou-Yang HF, Huang Y, Hu XB, Wu CG. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells. Exp Biol Med (Maywood) 2011;236(12):1461–1467. doi: 10.1258/ebm.2011.011221.
    1. Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol. 2010;299(6):L760–L770. doi: 10.1152/ajplung.00182.2009.
    1. Sun YQ, Deng MX, He J, Zeng QX, Wen W, Wong DS, Tse HF, Xu G, Lian Q, Shi J, Fu QL. Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice. Stem Cells. 2012;30(12):2692–2699. doi: 10.1002/stem.1241.
    1. Xu T, Zhou Y, Qiu L, Do DC, Zhao Y, Cui Z, Wang H, Liu X, Saradna A, Cao X, Wan M, Gao P. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells. J Immunol. 2015;195(12):5539–5550. doi: 10.4049/jimmunol.1501198.
    1. Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007;104(26):11002–11007. doi: 10.1073/pnas.0704421104.
    1. Chang YS, Oh W, Choi SJ, Sung DK, Kim SY, Choi EY, Kang S, Jin HJ, Yang YS, Park WS. Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats. Cell Transplant. 2009;18(8):869–886. doi: 10.3727/096368909X471189.
    1. Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009;175(1):303–313. doi: 10.2353/ajpath.2009.080629.
    1. Tropea KA, Leder E, Aslam M, Lau AN, Raiser DM, Lee JH, Balasubramaniam V, Fredenburgh LE, Alex MS, Kourembanas S, Kim CF. Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2012;302(9):L829–L837. doi: 10.1152/ajplung.00347.2011.
    1. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685–1693. doi: 10.1056/NEJMoa050333.
    1. Danchuk S, Ylostalo JH, Hossain F, Sorge R, Ramsey A, Bonvillain RW, Lasky JA, Bunnell BA, Welsh DA, Prockop DJ, Sullivan DE. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-alpha-induced protein 6. Stem Cell Res Ther. 2011;2(3):27. doi: 10.1186/scrt68.
    1. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007;179(3):1855–1863. doi: 10.4049/jimmunol.179.3.1855.
    1. Ionescu L, Byrne RN, Van Haaften T, Vadivel A, Alphonse RS, Rey-Parra GJ, Weissmann G, Hall A, Eaton F, Thebaud B. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012;303(11):L967–L977. doi: 10.1152/ajplung.00144.2011.
    1. Gupta N, Krasnodembskaya A, Kapetanaki M, Mouded M, Tan X, Serikov V, Matthay MA. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012;67(6):533–539. doi: 10.1136/thoraxjnl-2011-201176.
    1. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010;28(12):2229–2238. doi: 10.1002/stem.544.
    1. Lee JW, Krasnodembskaya A, McKenna DH, Song Y, Abbott J, Matthay MA. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am J Respir Crit Care Med. 2013;187(7):751–760. doi: 10.1164/rccm.201206-0990OC.
    1. Monsel A, Zhu YG, Gennai S, Hao Q, Hu S, Rouby JJ, Rosenzwajg M, Matthay MA, Lee JW. Therapeutic Effects of Human Mesenchymal Stem Cell-derived Microvesicles in Severe Pneumonia in Mice. Am J Respir Crit Care Med. 2015;192(3):324–336. doi: 10.1164/rccm.201410-1765OC.
    1. Chan MC, Kuok DI, Leung CY, Hui KP, Valkenburg SA, Lau EH, Nicholls JM, Fang X, Guan Y, Lee JW, Chan RW, Webster RG, Matthay MA, Peiris JS. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. Proc Natl Acad Sci U S A. 2016;113(13):3621–3626. doi: 10.1073/pnas.1601911113.
    1. Darwish I, Banner D, Mubareka S, Kim H, Besla R, Kelvin DJ, Kain KC, Liles WC. Mesenchymal stromal (stem) cell therapy fails to improve outcomes in experimental severe influenza. PLoS One. 2013;8(8) doi: 10.1371/journal.pone.0071761.
    1. Gotts JE, Abbott J, Matthay MA. Influenza causes prolonged disruption of the alveolar-capillary barrier in mice unresponsive to mesenchymal stem cell therapy. Am J Physiol Lung Cell Mol Physiol. 2014;307(5):L395–L406. doi: 10.1152/ajplung.00110.2014.
    1. Hall SR, Tsoyi K, Ith B, Padera RF, Jr, Lederer JA, Wang Z, Liu X, Perrella MA. Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils. Stem Cells. 2013;31(2):397–407. doi: 10.1002/stem.1270.
    1. Raffaghello L, Bianchi G, Bertolotto M, Montecucco F, Busca A, Dallegri F, Ottonello L, Pistoia V. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells. 2008;26(1):151–162. doi: 10.1634/stemcells.2007-0416.
    1. Zheng G, Huang L, Tong H, Shu Q, Hu Y, Ge M, Deng K, Zhang L, Zou B, Cheng B, Xu J. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study. Respir Res. 2014;15:39. doi: 10.1186/1465-9921-15-39.
    1. Chambers DC, Enever D, Ilic N, Sparks L, Whitelaw K, Ayres J, Yerkovich ST, Khalil D, Atkinson KM, Hopkins PM. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014;19(7):1013–1018. doi: 10.1111/resp.12343.

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