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Published in: Clinical Rheumatology 1/2012

01-01-2012 | Brief Report

Allogeneic mesenchymal stem cells transplantation in patients with refractory RA

Authors: Jun Liang, Xia Li, Huayong Zhang, Dandan Wang, Xuebing Feng, Hong Wang, Bingzhu Hua, Bujun Liu, Lingyun Sun

Published in: Clinical Rheumatology | Issue 1/2012

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Abstract

This study aimed to determine the safety and efficacy of allogeneic mesenchymal stem cells transplantation (MSCT) in refractory rheumatoid arthritis (RA). Four patients with persistently active RA underwent MSCT. The outcome was evaluated by changes in the visual analog scale (VAS 100 mm) pain score, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and 28-joint disease activity score (DAS-28). Three of four patients received a reduction in ESR, DAS-28, and pain VAS score at 1 and 6 months after transplantation. Two of the three had a European League Against Rheumatism (EULAR) moderate response at 6 months but experienced a relapse at 7 and 23 months, respectively. Two patients had no EULAR response to MSCT. No one had achieved the DAS-28-defined remission in the follow-up period. No serious adverse events were reported. Allogeneic MSCT is a safe treatment in severe and resistant RA, but the effectiveness needs to be clarified.
Literature
1.
go back to reference Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285PubMedCrossRef Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285PubMedCrossRef
2.
go back to reference Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S, Dougados M (2007) Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology 46(2):327–334PubMedCrossRef Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S, Dougados M (2007) Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology 46(2):327–334PubMedCrossRef
3.
go back to reference Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedCrossRef Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedCrossRef
4.
go back to reference Schwartz RE, Reyes M, Koodie L et al (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109:1291–1302PubMed Schwartz RE, Reyes M, Koodie L et al (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109:1291–1302PubMed
5.
go back to reference Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20PubMedCrossRef Pittenger MF, Martin BJ (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95:9–20PubMedCrossRef
6.
go back to reference Beck PL, Rosenberg IM, Xavier RJ, Koh T, Wong JF, Podolsky DK (2003) Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells. Am J Pathol 162:597–608PubMedCrossRef Beck PL, Rosenberg IM, Xavier RJ, Koh T, Wong JF, Podolsky DK (2003) Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells. Am J Pathol 162:597–608PubMedCrossRef
7.
go back to reference Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50(Suppl 1):S24–S33PubMedCrossRef Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50(Suppl 1):S24–S33PubMedCrossRef
8.
go back to reference Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW et al (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549PubMedCrossRef Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW et al (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549PubMedCrossRef
9.
go back to reference Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506PubMedCrossRef Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506PubMedCrossRef
10.
go back to reference Jiang XX, Zhang Y, Liu B et al (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126PubMedCrossRef Jiang XX, Zhang Y, Liu B et al (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105:4120–4126PubMedCrossRef
11.
go back to reference Sotiropoulou PA, Perez SA, Gritzapis AD et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85PubMedCrossRef Sotiropoulou PA, Perez SA, Gritzapis AD et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85PubMedCrossRef
12.
go back to reference Potian JA, Aviv H, Ponzio NM et al (2003) Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 171:3426–3434PubMed Potian JA, Aviv H, Ponzio NM et al (2003) Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 171:3426–3434PubMed
13.
go back to reference Beyth S, Borovsky Z, Mevorach D et al (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105:2214–2219PubMedCrossRef Beyth S, Borovsky Z, Mevorach D et al (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105:2214–2219PubMedCrossRef
14.
go back to reference Liu Y, Mu R, Wang S et al (2010) Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther 12(6):R210PubMedCrossRef Liu Y, Mu R, Wang S et al (2010) Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther 12(6):R210PubMedCrossRef
15.
go back to reference Oshita K, Yamaoka K, Udagawa N et al (2011) Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis Rheum 63(6):1658–1667PubMedCrossRef Oshita K, Yamaoka K, Udagawa N et al (2011) Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis Rheum 63(6):1658–1667PubMedCrossRef
16.
go back to reference González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60(4):1006–1019PubMedCrossRef González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60(4):1006–1019PubMedCrossRef
17.
go back to reference Lu LL, Liu YJ, Yang SG et al (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91:1017–1026PubMed Lu LL, Liu YJ, Yang SG et al (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91:1017–1026PubMed
18.
go back to reference Le Blanc K, Frassoni F, Ball L et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371(9624):1579–1586PubMedCrossRef Le Blanc K, Frassoni F, Ball L et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371(9624):1579–1586PubMedCrossRef
19.
go back to reference Dudics V, Kunstár A, Kovács J et al (2009) Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis: measurements in a microculture system. Cells Tissues Organs 189(5):307–316PubMedCrossRef Dudics V, Kunstár A, Kovács J et al (2009) Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis: measurements in a microculture system. Cells Tissues Organs 189(5):307–316PubMedCrossRef
20.
go back to reference Sotiropoulou PA, Sonia A et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85PubMedCrossRef Sotiropoulou PA, Sonia A et al (2006) Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 24:74–85PubMedCrossRef
21.
go back to reference Klyushnenkova E, Mosca JD, Zernetkina V et al (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47–57PubMedCrossRef Klyushnenkova E, Mosca JD, Zernetkina V et al (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47–57PubMedCrossRef
22.
go back to reference Corcione A, Benvenuto F, Ferretti E et al (2006) Human mesenchymal stem cells modulate B cell functions. Blood 107:367–372PubMedCrossRef Corcione A, Benvenuto F, Ferretti E et al (2006) Human mesenchymal stem cells modulate B cell functions. Blood 107:367–372PubMedCrossRef
23.
go back to reference Zheng ZH, Li XY, Ding J, Jia JF, Zhu P (2008) Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. Rheumatology Oxford 47(1):22–30PubMedCrossRef Zheng ZH, Li XY, Ding J, Jia JF, Zhu P (2008) Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. Rheumatology Oxford 47(1):22–30PubMedCrossRef
24.
go back to reference Jones E, Churchman SM, English A et al (2010) Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann Rheum Dis 69(2):450–457PubMedCrossRef Jones E, Churchman SM, English A et al (2010) Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann Rheum Dis 69(2):450–457PubMedCrossRef
Metadata
Title
Allogeneic mesenchymal stem cells transplantation in patients with refractory RA
Authors
Jun Liang
Xia Li
Huayong Zhang
Dandan Wang
Xuebing Feng
Hong Wang
Bingzhu Hua
Bujun Liu
Lingyun Sun
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
Clinical Rheumatology / Issue 1/2012
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-011-1816-0

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