In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.
This single-center, randomized, triple-blind, placebo-controlled phase 1/2 clinical trial randomized RA patients with knee involvement to receive either an intra-articular knee implantation of 40 million autologous bone marrow–derived MSCs per joint or normal saline (placebo). Patients were followed up for 12 months to assess therapy outcomes.
A total of 30 patients, 15 in the MSC group and 15 in the placebo group, enrolled in this study. There were no adverse effects reported after MSC administration or during follow-up. Patients who received MSCs had superior findings according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), time to jelling and pain-free walking distance. However, this improvement could not be significantly sustained beyond 12 months. The MSC group exhibited improved standing time (P = 0.01). In addition, the MSCs appeared to contribute to reductions in methotrexate and prednisolone use.
Intra-articular knee implantation of MSCs appeared to be safe and well tolerated. In addition, we observed a trend toward clinical efficacy. These results, in our opinion, have justified the need for further investigations over an extended assessment period with larger numbers of RA patients who have knee involvement.
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- The pathogenesis of rheumatoid arthritis.N Engl J Med. 2011; 365: 2205-2219
- Pathogenetic insights from the treatment of rheumatoid arthritis.Lancet. 2017; 389: 2328-2337
- Radiological damage in patients with rheumatoid arthritis on sustained remission.Ann Rheum Dis. 2007; 66: 358-363
- Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids.Rheumatol Int. 2001; 20: 65-69
- Rheumatoid arthritis is associated with higher ninety-day hospital readmission rates compared to osteoarthritis after hip or knee arthroplasty: a cohort study.Arthritis Care Res (Hoboken). 2015; 67: 718-724
- Impact of total knee arthroplasty as assessed using patient-reported pain and health-related quality of life indices: rheumatoid arthritis versus osteoarthritis.Arthritis Rheumatol. 2015; 67: 2503-2511
- Clinical trials with mesenchymal stem cells: an update.Cell Transplant. 2016; 25: 829-848
- Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis.Arthritis Rheum. 2007; 56: 1175-1186
- Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells.Arthritis Rheum. 2009; 60: 1006-1019
- Use of immune modulation by human adipose-derived mesenchymal stem cells to treat experimental arthritis in mice.Am J Transl Res. 2017; 9: 2595-2607
- Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans.Stem Cells. 2009; 27: 1421-1432
- Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.Cell Mol Immunol. 2008; 5: 417-424
- Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation.Arthritis Rheum. 2012; 64: 243-253
- Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses.Gastroenterology. 2009; 136: 978-989
- Topical implantation of mesenchymal stem cells has beneficial effects on healing of experimental colitis in rats.J Pharmacol Exp Ther. 2008; 326: 523-531
- Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy.Blood. 2005; 106: 1755-1761
- 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: 5994-6002
- Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results.Transplantation. 2014; 97: e66-e68
- Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial.Transplantation. 2015; 99: 1681-1690
- Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel(R)): preclinical and clinical trial in osteoarthritis of the knee joint.Arthritis Res Ther. 2016; 18: 301
- Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II).J Transl Med. 2016; 14: 246
- Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis.Arch Iran Med. 2012; 15: 422-428
- Allogeneic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study.Ann Rheum Dis. 2010; 69: 1423-1429
- Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study.Arthritis Res Ther. 2014; 16: R79
- Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial.Lancet. 2016; 388: 1281-1290
- Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study.Curr Stem Cell Res Ther. 2012; 7: 407-414
- Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.Lancet Neurol. 2012; 11: 150-156
- Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease.Biol Blood Marrow Transplant. 2014; 20: 1580-1585
- Phase II multicenter, randomized, double-blind controlled study of efficacy and safety of umbilical cord-derived mesenchymal stromal cells in the prophylaxis of chronic graft-versus-host disease after HLA-haploidentical stem-cell transplantation.J Clin Oncol. 2016; 34: 2843-2850
- Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy.Stem Cells Dev. 2013; 22: 3192-3202
- Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial.Ann Rheum Dis. 2017; 76: 196-202
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.Cytotherapy. 2006; 8: 315-317
- 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: 336-344
- Reciprocal interactions between human mesenchymal stem cells and gammadelta T cells or invariant natural killer T cells.Stem Cells. 2009; 27: 693-702
- Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: a meta-analysis.PLoS ONE. 2017; 12 (e0175449)
Published online: February 07, 2018
Accepted: December 27, 2017
Received: June 17, 2017
© 2018 Published by Elsevier Inc. on behalf of International Society for Cellular Therapy.