Immunomodulation by mesenchymal stem cells and clinical experience

Journal of Internal Medicine - Tập 262 Số 5 - Trang 509-525 - 2007
Katarina Le Blanc1, O Ringdén
1Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. [email protected]

Tóm tắt

Abstract

Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T‐cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T‐cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy‐resistant severe acute graft‐versus‐host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders.

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Tài liệu tham khảo

10.1097/00007890-196803000-00009

10.1016/S0074-7696(08)60092-3

Friedenstein AJ, 1987, Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers, Cell Tissue Kinet, 20, 263

Owen M, 1988, Stromal stem cells: marrow‐derived osteogenic precursors, Ciba Found Symp, 136, 42

10.1046/j.1365-2141.2000.01986.x

10.1182/blood.V98.8.2396

10.1016/S0301-472X(02)00820-2

10.1159/000071150

Friedenstein AJ, 1970, The development of fibroblast colonies in monolayer cultures of guinea‐pig bone marrow and spleen cells, Cell Tissue Kinet, 3, 393

Keilis‐Borok IV, 1971, Dynamics of formation of fibroblast colonies in monolayer cultures of bone marrow according to H3‐thymidine incorporation data, Tsitologiia, 13, 1402

10.1007/BF00800170

10.1182/blood.V56.2.289.289

10.1182/blood.V78.1.55.55

10.1182/blood.V84.12.4164.bloodjournal84124164

Simmons PJ, 1994, Isolation, characterization and functional activity of human marrow stromal progenitors in hemopoiesis, Prog Clin Biol Res, 389, 271

10.1182/blood.V85.4.929.bloodjournal854929

10.1002/art.10696

10.1242/jcs.00369

10.1016/S0301-472X(00)00160-0

10.1089/107632702320934001

10.1002/jor.1100090504

Muraglia A, 2000, Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model, J Cell Sci, 113, 1161, 10.1242/jcs.113.7.1161

10.1634/stemcells.19-5-408

10.1016/0014-5793(96)00240-2

10.1038/81395

10.1073/pnas.0401558101

10.1002/jor.1100090504

10.1159/000047856

10.1002/jgm.452

10.1182/blood-2002-06-1830

10.1023/B:ABME.0000017545.84833.7c

10.2106/00004623-200310000-00010

10.1126/science.1088757

10.1161/hc0102.101442

10.1002/art.11365

10.1016/S0074-7696(03)28001-3

Deng Y, 2003, Efficiency of adenoviral vector mediated CTLA4Ig gene delivery into mesenchymal stem cells, Chin Med J (Engl), 116, 1649

10.1073/pnas.1432929100

10.1002/(SICI)1097-4652(199603)166:3<585::AID-JCP13>3.0.CO;2-6

10.1002/(SICI)1097-4652(199807)176:1<57::AID-JCP7>3.0.CO;2-7

10.1016/S0301-472X(99)00090-9

10.1210/endo.140.8.6880

10.1016/S0301-472X(03)00042-0

10.1016/S0301-472X(03)00202-9

10.1038/sj.bmt.1704400

10.1016/S0301-472X(01)00769-X

10.1182/blood-2002-07-2104

10.1046/j.1365-3083.2003.01176.x

10.1097/01.TP.0000045055.63901.A9

10.1152/ajprenal.00007.2005

10.1182/blood-2005-04-1496

10.1002/(SICI)1097-4652(199910)181:1<67::AID-JCP7>3.0.CO;2-C

10.1016/S0301-472X(00)00482-3

10.1016/S0165-2478(03)00108-1

10.1016/S0301-472X(03)00110-3

10.1007/s11373-004-8183-7

10.4049/jimmunol.171.7.3426

10.1182/blood-2004-07-2921

10.1111/j.0300-9475.2004.01483.x

10.1097/01.TP.0000082540.43730.80

Angoulvant D, 2004, Human mesenchymal stem cells suppress induction of cytotoxic response to alloantigens, Biorheology, 41, 469

10.1182/blood.V99.10.3838

10.1016/j.yexcr.2004.12.013

10.1016/j.transproceed.2004.11.090

10.1182/blood-2004-09-3696

10.4049/jimmunol.155.3.1151

10.1016/j.bbmt.2004.11.005

10.1182/blood-2004-04-1559

Maccario R, 2005, 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, 90, 516

10.1016/j.exphem.2005.05.002

10.1182/blood-2003-04-1193

10.1002/eji.200425405

10.1126/science.281.5380.1191

10.1182/blood-2003-11-3909

10.4049/jimmunol.173.7.4352

10.1002/jcp.20031

10.1182/blood-2005-07-2657

10.1097/00007890-197108000-00001

10.1182/blood-2004-02-0586

10.1089/154732804323099190

10.1016/j.immuni.2004.10.012

10.1002/eji.1830080110

10.1111/j.1365-3083.2007.01905.x

10.1161/01.CIR.0000070931.62772.4E

10.1038/sj.leu.2402786

10.1097/01.TP.0000159029.48678.93

10.1182/blood-2005-03-1004

10.1073/pnas.95.7.3908

10.1016/S0003-4975(02)03591-9

10.1016/j.jtcvs.2003.07.037

10.1161/01.CIR.0000124222.16321.26

10.1073/pnas.95.3.1142

Lazarus HM, 1995, Ex vivo expansion and subsequent infusion of human bone marrow‐derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use, Bone Marrow Transplant, 16, 557

10.1200/JCO.2000.18.2.307

10.1016/S0301-472X(99)00101-0

10.1097/00007890-198410000-00001

Krivit W, 1996, Handbook of Clinical Neurology, 87

10.1038/sj.bmt.1703650

Sillence DO, 1979, Clinical variability in osteogenesis imperfecta‐variable expressivity or genetic heterogeneity, Birth Defects Orig Artic Ser, 15, 113

10.1038/6529

10.1182/blood.V97.5.1227

10.1073/pnas.132252399

10.1046/j.1365-2141.2002.03767.x

10.1038/sj.leu.2404777

10.1016/S0301-472X(00)00635-4

10.1016/j.bbmt.2005.02.001

10.1016/j.bbmt.2004.06.001

10.1016/S0140-6736(04)16104-7

10.1097/01.tp.0000214462.63943.14

Le Blanc K, 2006, Mesenchymal stem cells for treatment of severe graft‐versus‐host disease, Blood, 108, 753a, 10.1182/blood.V108.11.5304.5304

10.1038/sj.leu.2404833

10.1038/sj.bmt.1705368

10.1182/blood.V75.3.555.555

10.1056/NEJM197905103001902

Ringden O, 1996, Graft‐versus‐leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation, Bone Marrow Transplant, 18, 921

10.3109/10428199609045715

10.1097/01.TP.0000048488.35010.95