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11.01.2024 | ORIGINAL ARTICLE

Umbilical cord mesenchymal stem cells transplantation in patients with systemic sclerosis: a 5-year follow-up study

verfasst von: Mihribangvl Alip, Dandan Wang, Shengnan Zhao, Siqi Li, Dongdong Zhang, Xiaoxiao Duan, Shiying Wang, Bingzhu Hua, Hong Wang, Huayong Zhang, Xuebing Feng, Lingyun Sun

Erschienen in: Clinical Rheumatology | Ausgabe 3/2024

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Abstract

Objective

To assess the long-term safety and efficacy of umbilical cord mesenchymal stem cells transplantation (UMSCT) in patients with systemic sclerosis (SSc).

Methods

Forty-one patients with moderate to severe SSc underwent UMSCT at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2009 to 2017. In this study, we conducted a longitudinal and retrospective analysis and compared the clinical and laboratory manifestations before and after UMSCT. The main outcome of the study was overall survival. We evaluated changes in the modified Rodnan Skin Score (mRSS), as well as the changes in the pulmonary examination by using high-resolution computed tomography (HRCT) and ultrasound cardiogram (UCG). Additionally, we assessed the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the severity of peripheral vascular involvement during the first year after treatment.

Results

The overall 5-year survival rate was 92.7% (38 out of 41 patients). Following UMSCT, the mean mRSS significantly decreased from 18.68 (SD = 7.26, n = 41) at baseline to 13.95 (SD = 8.49, n = 41), 13.29 (SD = 7.67, n = 38), and 12.39 (SD = 8.49, n = 38) at 1, 3, and 5 years, respectively. Improvement or stability in HRCT images was observed in 72.0% of interstitial lung disease (ILD) patients. Pulmonary arterial hypertension (PAH) remained stable in 5 out of 8 patients at the 5-year follow-up. No adverse events related to UMSCT were observed in any of the patients during the follow-up period.

Conclusion

UMSCT may provide a safe and feasible treatment option for patients with moderate to severe SSc based on long-term follow-up data. The randomized controlled study will further confirm the clinical efficacy of UMSCT in SSc.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT00962923.

Key Point

• UMSCT is safe and effective for SSc patients.

Nur mit Berechtigung zugänglich

Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, Distler O et al (2017) Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 76(8):1327–1339. https://doi.org/10.1136/annrheumdis-2016-209909CrossRefPubMed

Denton CP, Khanna D (2017) Systemic sclerosis. Lancet (London, England) 390(10103):1685–1699. https://doi.org/10.1016/S0140-6736(17)30933-9CrossRefPubMed

Hachulla E, Launay D (2011) Diagnosis and classification of systemic sclerosis. Clin Rev Allergy Immunol 40(2):78–83. https://doi.org/10.1007/s12016-010-8198-yCrossRefPubMed

Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, Clements P et al (2009) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68(5):620–628. https://doi.org/10.1136/ard.2008.096677CrossRefPubMed

Velier M, Daumas A, Simoncini S, Arcani R, Magalon J, Benyamine A, Granel B et al (2021) Combining systemic and locally applied cellular therapies for the treatment of systemic sclerosis. Bone Marrow Transplant. https://doi.org/10.1038/s41409-021-01492-7CrossRefPubMed

Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, Marjanovic Z, Burman J et al (2017) Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv 1(27):2742–2755. https://doi.org/10.1182/bloodadvances.2017010041CrossRefPubMedPubMedCentral

Farge D, Loisel S, Lansiaux P, Tarte K (2021) Mesenchymal stromal cells for systemic sclerosis treatment. Autoimmun Rev 20(3):102755. https://doi.org/10.1016/j.autrev.2021.102755CrossRefPubMed

Spierings J, van Rhijn-Brouwer FCC, van Laar JM (2018) Hematopoietic stem-cell transplantation in systemic sclerosis: an update. Curr Opin Rheumatol 30(6):541–547. https://doi.org/10.1097/BOR.0000000000000541CrossRefPubMed

Strunz P-P, Froehlich M, Gernert M, Schwaneck EC, Fleischer A, Pecher A-C, Tony H-P et al (2021) Immunological adverse events after autologous hematopoietic stem cell transplantation in systemic sclerosis patients. Front Immunol 12. https://doi.org/10.3389/fimmu.2021.723349

10.

Burt RK, Farge D (2018) Systemic sclerosis: autologous HSCT is efficacious, but can we make it safer? Nat Rev Rheumatol 14(4):189–191. https://doi.org/10.1038/nrrheum.2018.34CrossRefPubMed

11.

Farge D, Burt RK, Oliveira MC, Mousseaux E, Rovira M, Marjanovic Z, de Vries-Bouwstra J et al (2017) Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners. Bone Marrow Transplant 52(11):1495–1503. https://doi.org/10.1038/bmt.2017.56CrossRefPubMedPubMedCentral

12.

de Castro LL, Lopes-Pacheco M, Weiss DJ, Cruz FF, Rocco PRM (2019) Current understanding of the immunosuppressive properties of mesenchymal stromal cells. J Mol Med (Berl) 97(5):605–618. https://doi.org/10.1007/s00109-019-01776-yCrossRefPubMed

13.

Le Blanc K, Davies LC (2015) Mesenchymal stromal cells and the innate immune response. Immunol Lett 168(2):140–146. https://doi.org/10.1016/j.imlet.2015.05.004CrossRefPubMed

14.

Li W, Chen W, Huang S, Tang X, Yao G, Sun L (2020) Mesenchymal stem cells enhance pulmonary antimicrobial immunity and prevent following bacterial infection. Stem Cells Int 2020:3169469. https://doi.org/10.1155/2020/3169469CrossRefPubMedPubMedCentral

15.

Wang D, Zhang H, Liang J, Wang H, Hua B, Feng X, Gilkeson GS et al (2018) A long-term follow-up study of allogeneic mesenchymal stem/stromal cell transplantation in patients with drug-resistant systemic lupus erythematosus. Stem Cell Rep 10(3):933–941. https://doi.org/10.1016/j.stemcr.2018.01.029CrossRef

16.

Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y et al (2010) Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 69(8):1423–1429. https://doi.org/10.1136/ard.2009.123463CrossRefPubMed

17.

Xu J, Wang D, Liu D, Fan Z, Zhang H, Liu O, Ding G et al (2012) Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood 120(15):3142–3151. https://doi.org/10.1182/blood-2011-11-391144CrossRefPubMedPubMedCentral

18.

Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B et al (2012) Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol 31(1):157–161. https://doi.org/10.1007/s10067-011-1816-0CrossRefPubMed

19.

Zhang H, Liang J, Tang X, Wang D, Feng X, Wang F, Hua B et al (2017) Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis. Arthritis Res Ther 19(1):165. https://doi.org/10.1186/s13075-017-1373-2CrossRefPubMedPubMedCentral

20.

Granel B, Daumas A, Jouve E, Harle JR, Nguyen PS, Chabannon C, Colavolpe N et al (2015) Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis 74(12):2175–2182. https://doi.org/10.1136/annrheumdis-2014-205681CrossRefPubMed

21.

Guillaume-Jugnot P, Daumas A, Magalon J, Jouve E, Nguyen PS, Truillet R, Mallet S et al (2016) Autologous adipose-derived stromal vascular fraction in patients with systemic sclerosis: 12-month follow-up. Rheumatology (Oxford) 55(2):301–306. https://doi.org/10.1093/rheumatology/kev323CrossRefPubMed

22.

van Rhijn-Brouwer FCC, Gremmels H, Fledderus JO, Schuurman AH, Bonte-Mineur F, Vonk MC, Voskuyl AE et al (2018) A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol. BMJ Open 8(8):e020479. https://doi.org/10.1136/bmjopen-2017-020479CrossRefPubMedPubMedCentral

23.

Hachulla E, Gressin V, Guillevin L, Carpentier P, Diot E, Sibilia J, Kahan A et al (2005) Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum 52(12):3792–3800. https://doi.org/10.1002/art.21433CrossRefPubMed

24.

Bruera S, Sidanmat H, Molony DA, Mayes MD, Suarez-Almazor ME, Krause K, Lopez-Olivo MA (2022) Stem cell transplantation for systemic sclerosis. Cochrane Database Syst Rev (7). https://doi.org/10.1002/14651858.CD011819.pub2

25.

Escobar-Soto CH, Mejia-Romero R, Aguilera N, Alzate-Granados JP, Mendoza-Pinto C, Munguia-Realpozo P, Mendez-Martinez S et al (2021) Human mesenchymal stem cells for the management of systemic sclerosis. Syst Rev Autoimmun Rev 20(6):102831. https://doi.org/10.1016/j.autrev.2021.102831CrossRef

26.

Steen VD, Medsger TA Jr (2001) Improvement in skin thickening in systemic sclerosis associated with improved survival. Arthritis Rheum 44(12):2828–2835. https://doi.org/10.1002/1529-0131(200112)44:12%3c2828::aid-art470%3e3.0.co;2-uCrossRefPubMed

27.

van Laar JM, Sullivan K (2013) Stem cell transplantation in systemic sclerosis. Curr Opin Rheumatol 25(6):719–725. https://doi.org/10.1097/01.bor.0000434669.32150.acCrossRefPubMed

28.

Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, Craig R et al (2011) Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. The Lancet 378(9790):498–506. https://doi.org/10.1016/s0140-6736(11)60982-3CrossRef

29.

van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ et al (2014) Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis. Jama 311(24). https://doi.org/10.1001/jama.2014.6368

30.

Burt RK, Oliveira MC, Shah SJ, Moraes DA, Simoes B, Gheorghiade M, Schroeder J et al (2013) Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis. Lancet 381(9872):1116–1124. https://doi.org/10.1016/S0140-6736(12)62114-XCrossRefPubMed

31.

Yuan YP, Yuan P, Su YL, Jiang R, Zhang R, He J, Qiu HL et al (2022) Clinical phenotypes, hemodynamic characteristics and prognosis of Chinese patients with systemic sclerosis-associated precapillary pulmonary hypertension: a retrospective study. Clin Rheumatol 41(6):1675–1686. https://doi.org/10.1007/s10067-021-06016-8CrossRefPubMed

32.

Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD et al (2018) Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med 378(1):35–47. https://doi.org/10.1056/nejmoa1703327CrossRefPubMedPubMedCentral

33.

Wang D, Akiyama K, Zhang H, Yamaza T, Li X, Feng X, Wang H et al (2012) Double allogenic mesenchymal stem cells transplantations could not enhance therapeutic effect compared with single transplantation in systemic lupus erythematosus. Clin Dev Immunol 2012:273291. https://doi.org/10.1155/2012/273291CrossRefPubMedPubMedCentral

34.

Szekanecz Z, Aleksza M, Antal-Szalmas P, Soltesz P, Veres K, Szanto S, Szabo Z et al (2009) Combined plasmapheresis and high-dose intravenous immunoglobulin treatment in systemic sclerosis for 12 months: follow-up of immunopathological and clinical effects. Clin Rheumatol 28(3):347–350. https://doi.org/10.1007/s10067-008-1062-2CrossRefPubMed

35.

Rozier P, Maria A, Goulabchand R, Jorgensen C, Guilpain P, Noel D (2018) Mesenchymal stem cells in systemic sclerosis: allogenic or autologous approaches for therapeutic use? Front Immunol 9:2938. https://doi.org/10.3389/fimmu.2018.02938CrossRefPubMedPubMedCentral

36.

Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210CrossRefPubMedPubMedCentral

37.

Michel L, Farge D, Baraut J, Marjanovic Z, Jean-Louis F, Porcher R, Grigore EI et al (2016) Evolution of serum cytokine profile after hematopoietic stem cell transplantation in systemic sclerosis patients. Bone Marrow Transplant 51(8):1146–1149. https://doi.org/10.1038/bmt.2016.77CrossRefPubMed

38.

Zhang W, Xu JR, Lu Q, Ye S, Liu XS (2011) High-resolution magnetic resonance angiography of digital arteries in SSc patients on 3 Tesla: preliminary study. Rheumatology (Oxford) 50(9):1712–1719. https://doi.org/10.1093/rheumatology/keq453CrossRefPubMed

39.

Rubio GA, Elliot SJ, Wikramanayake TC, Xia X, Pereira-Simon S, Thaller SR, Glinos GD et al (2018) Mesenchymal stromal cells prevent bleomycin-induced lung and skin fibrosis in aged mice and restore wound healing. J Cell Physiol 233(8):5503–5512. https://doi.org/10.1002/jcp.26418CrossRefPubMedPubMedCentral

40.

Maria ATJ, Maumus M, Le Quellec A, Jorgensen C, Noël D, Guilpain P (2017) Adipose-derived mesenchymal stem cells in autoimmune disorders: state of the art and perspectives for systemic sclerosis. Clin Rev Allergy Immunol 52(2):234–259. https://doi.org/10.1007/s12016-016-8552-9CrossRefPubMed

41.

Maria AT, Toupet K, Maumus M, Fonteneau G, Le Quellec A, Jorgensen C, Guilpain P et al (2016) Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis. J Autoimmun 70:31–39. https://doi.org/10.1016/j.jaut.2016.03.013CrossRefPubMed

42.

Lee SH, Jang AS, Kim YE, Cha JY, Kim TH, Jung S, Park SK et al (2010) Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respir Res 11:16. https://doi.org/10.1186/1465-9921-11-16CrossRefPubMedPubMedCentral

43.

Guiducci S, Manetti M, Romano E, Mazzanti B, Ceccarelli C, Dal Pozzo S, Milia AF et al (2011) Bone marrow-derived mesenchymal stem cells from early diffuse systemic sclerosis exhibit a paracrine machinery and stimulate angiogenesis in vitro. Ann Rheum Dis 70(11):2011–2021. https://doi.org/10.1136/ard.2011.150607CrossRefPubMed

Titel: Umbilical cord mesenchymal stem cells transplantation in patients with systemic sclerosis: a 5-year follow-up study
verfasst von: Mihribangvl Alip
Dandan Wang
Shengnan Zhao
Siqi Li
Dongdong Zhang
Xiaoxiao Duan
Shiying Wang
Bingzhu Hua
Hong Wang
Huayong Zhang
Xuebing Feng
Lingyun Sun
Publikationsdatum: 11.01.2024
Verlag: Springer International Publishing
Erschienen in: Clinical Rheumatology / Ausgabe 3/2024
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-024-06865-z

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Umbilical cord mesenchymal stem cells transplantation in patients with systemic sclerosis: a 5-year follow-up study