Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen‐induced arthritis

Wiley - Tập 56 Số 4 - Trang 1175-1186 - 2007
Andrea Augello1, Roberta Tasso2, Simone Negrini2, Ranieri Cancedda3, Giuseppina Pennesi2
1Department of Oncology, Biology and Genetics, University of Genoa, National Institute for Cancer Research, Genoa, Italy.
2Univ. of Genoa, Genoa, , Italy
3National Institute for Cancer Research, and University of Genoa, Genoa, Italy

Tóm tắt

AbstractObjectiveMesenchymal stem cells (MSCs) are precursors of tissue of mesenchymal origin, but they also have the capacity to regulate the immune response by suppressing T and B lymphocyte proliferation in a non–major histocompatibility complex–restricted manner. Use of MSCs as immunosuppressant agents in autoimmune diseases has been proposed and successfully tested in animal models. We explored the feasibility of using allogeneic MSCs as therapy for collagen‐induced arthritis, a mouse model for human rheumatoid arthritis.MethodsDBA/1 mice were immunized with type II collagen in Freund's complete adjuvant, and some of the animals received an intraperitoneal injection of allogeneic MSCs.ResultsA single injection of MSCs prevented the occurrence of severe, irreversible damage to bone and cartilage. MSCs induced hyporesponsiveness of T lymphocytes as evidenced by a reduction in active proliferation, and modulated the expression of inflammatory cytokines. In particular, the serum concentration of tumor necrosis factor α was significantly decreased. MSCs exerted their immunomodulatory function by educating antigen‐specific Tregs.ConclusionOur results suggest an effective new therapeutic approach to target the pathogenic mechanism of autoimmune arthritis using allogeneic MSCs. However, further studies are required before these results can be translated to clinical settings.

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Tài liệu tham khảo

10.1111/j.0105-2896.2005.00322.x

10.1182/blood-2004-06-2480

10.1634/stemcells.19-3-180

10.1634/stemcells.22-4-487

10.1002/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C

10.1006/exnr.2000.7389

10.1046/j.0953-816x.2001.01814.x

10.1083/jcb.153.5.1133

10.1038/nature00870

10.4049/jimmunol.171.7.3426

10.1002/eji.200425405

10.1016/j.cyto.2005.11.003

10.1182/blood.V99.10.3838

10.1182/blood-2002-07-2104

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

10.1038/sj.bmt.1704400

10.1016/S0140-6736(04)16104-7

10.1182/blood-2005-04-1496

Ishida T, 1994, Requirement of donor‐derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation: complete prevention of recurrence of autoimmune diseases in MRL/MP‐lpr/lpr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor, J Immunol, 152, 3119, 10.4049/jimmunol.152.6.3119

Ciubotariu R, 1998, Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28− regulatory T cells, J Immunol, 161, 5193, 10.4049/jimmunol.161.10.5193

10.1038/nri821

10.1038/nri931

Seki N, 1992, 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, 148, 3093, 10.4049/jimmunol.148.10.3093

10.4049/jimmunol.165.3.1557

10.1002/art.11016

10.1073/pnas.0504388102

10.1038/nature01661

10.1016/j.transproceed.2005.09.122

10.1089/ten.2005.11.1198

10.1084/jem.20050085

10.1056/NEJMoa051907

10.1159/000088415

10.1111/j.1365-2141.2004.05298.x

10.1016/S0140-6736(04)16134-5

10.1159/000046561

10.1089/scd.2004.13.463

10.1002/art.21012

10.4049/jimmunol.175.8.5024

10.1056/NEJMp058236

10.1097/01.TP.0000128334.93343.B3

10.1056/NEJM200102013440516

10.1089/ten.2004.10.1093

10.1196/annals.1341.033

10.1172/JCI17856

10.1089/ten.2005.11.1115

10.1073/pnas.0406266102

10.1097/00001756-200103050-00025

10.1002/art.21195

10.1186/ar1500

10.1016/j.it.2005.07.007

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Wiley

Tập 56 Số 4

1175-1186

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