Mesenchymal stem cell therapy for refractory scleroderma: a report of 2 cases

Abstract

Abstract:We treated 2 patients with progressive, refractory scleroderma with a combined immunotherapy approach using plasmapheresis followed by rituximab and then intravenous umbilical-cord-derived allogeneic mesenchymal stem cells (MSCs). Both patients improved subjectively and objectively for over a year. Upon recurrence of their symptoms, the patients were treated again with allogeneic MSCs alone with a very good response. The combination was well tolerated and effective suggesting a large scale study may be warranted in progressive, refractory Scleroderma.

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases

“…Adverse events noted were upper respiratory tract infections reported by five patients and diarrhea reported by one patient during follow-up visits (Zhang et al, 2017). Results of two patients treated by Wehbe et al (2016) revealed that after one year of treatment, European Scleroderma Study Group activity index was reduced from 9.5 to 3.5 and 1.5, respectively (Wehbe et al, 2016) which correlates with the study of Zhang et al (2017) where the mean Modified Rodnan skin score improved from 20.1 ± 3.1 to 13.8 ± 10.2 in 14 patients.…”

“…Ten clinical studies have reported the use of hMSCs as advanced therapy for the treatment of systemic sclerosis in the last 5 years ( Table 9 ; Granel et al, 2015 ; Guillaume-Jugnot et al, 2015 ; Wehbe et al, 2016 ; Song et al, 2017 ; Virzì et al, 2017 ; Zhang et al, 2017 ; Van Rhijn-Brouwer et al, 2018 ; Park Y. et al, 2020 ) (NCT02975960 and NCT04356287). Among these studies, three studies were case reports ( Wehbe et al, 2016 ; Song et al, 2017 ; Virzì et al, 2017 ), in contrast to the rest which were clinical trials.…”

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

“…ADSVF-based treatments show similar outcomes in enhancing angiogenesis and wound healing causing better hand function and preventing amputation due to hand gangrene (Song et al 2017 ; Daumas et al 2017 ; Virzì et al 2017 ). Other studies have discussed the therapeutic function of UC-MSC in elevating hand and lung function as well as reducing collagen content in the skin in SSc patients (Liang et al 2018 ; Wehbe et al 2016 ; Zhang et al 2017 ). The clinical results and experimental conditions of clinical studies with a publication date of 2016 till now are provided in more detail in Table 4 .…”

“… ↑SHAQ score ↑CHFS score ↑grip strength ↑pinch strength ↓ RCS ↓DU NC in Mean global disease severity score NR UC-MSC (Zhang et al 2017 ) Clinical trial NR 14 patients affected by dcSSc ↓skin thickness ↑lung function (in 3 ILD affected patients) ↑ulcer healing ↓Serum anti-Scl70 autoantibody titer ↓TGFβ and VEGF levels NC in IFN-γ, IL-4 or IL-10 -upper respiratory tract infections -diarrhea (Liang et al 2018 ) Retrospective cohort NR 39 patients affected by SSc mesenchymal stem cell infusion is a safe therapy for patients with autoimmune diseases The incidence of Hyper acute (fever, headache, palpitation and so on) and acute (hair loss, facial rash and so on) adverse effects, transplantation-related mortality, infection and malignancy are not high. Survival rate in1 year after infusion is almost 70% (Wehbe et al 2016 ) Case report intravenous 2 affected by progressive, refractory scleroderma ↓dyspnea (first subject) Pulmonary hypertension was normalized (first subject) ↓skin contracture (first subject) pericardial effusion was resolved (first subject) ↓joint pain (second subject) ability to exert was normalized (second subject) ↓arthritis (second subject) ↓Raynaud’s phenomenon pain (second subject) ↑mobility and function(both subjects after second injection) NR PRP Platelet-Rich Plasma, IDU Indolent Digital Ulcers, IvMHISS Italian version of Mouth Handicap in Systemic Sclerosis Scale, VAS Visual Analogue Scale, AD Adipose, EQ-5D-5L EuroQol-5-Dimensions-5-Level, dcSSc Diffuse cutaneous Systemic Sclerosis, SSc Systemic Sclerosis, SHAQ Scleroderma Health Assessment Questionnaire, CHFS Cochin Hand Function Scale, RCS Raynaud’s Condition Score, DU Digital Ulcer, ILD Interstitial Lung Disease, TGFβ Transforming Growth Factor beta, VEGF Vascular Endothelial Growth Factor, IL Interleukin, MSC Mesenchymal Stem Cell, NR Not Reported, NC No Change …”

Stem Cell Therapies in Systemic Sclerosis: An Updated Review

“…However, evidence of their senescence does not represent a limitation for their potential use in cellular therapy and regenerative medicine to target scleroderma [67]. In 2 patients with refractory, progressive SSc, the combination of; plasmapheresis, rituximab, and IV MSCs derived from UCB resulted in clinical improvement lasting for more than 1 year [68]. In experimental models, it has been shown that the activity of inducible nitrous oxide synthase plays a crucial role in the antifibrotic activity of MSCs [64].…”