Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: Report of five cases

Keyszer, Gernot; Christopeit, Maximilian; Fick, Sylvia; Schendel, Marit; Taute, Bettina Maria; Behre, Gerhard; Müller, Lutz; Schmoll, H.-J.

doi:10.1002/art.30431

Cited by 82 publications

(52 citation statements)

References 13 publications

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“…The ulcers relapsed later and responded to bosentan [26]. This was followed by a later report by the same group of four further patients with SSc manifesting various degrees of internal organ involvement [27]. A. Tyndall / Immunology Letters xxx (2015) xxx-xxx The authors concluded cautiously that MSC improved the acral ulcers and to a lesser extent the skin thickening, but that given the heterogeneity of the clinical manifestations, larger studies were required.…”

Section: Systemic Sclerosismentioning

confidence: 95%

Mesenchymal stromal cells and rheumatic disorders

Tyndall

2015

Immunology Letters

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Section: Systemic Sclerosismentioning

confidence: 95%

Mesenchymal stromal cells and rheumatic disorders

Tyndall

2015

Immunology Letters

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“…1 2 Due to these properties, mesenchymal stromal cells (MSC) are being investigated for therapeutic and commercial applications. [3][4][5][6][7][8] In most cases, the hMSC are expanded in culture. Despite multiple cell divisions, they retain in vitro cell differentiation and antiproliferative properties.…”

Section: Introductionmentioning

confidence: 99%

FGF2 induces RANKL gene expression as well as IL1β regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells

et al. 2013

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ObjectiveHuman bone marrow mesenchymal stromal cells (hBM-MSC) are being applied in tissue regeneration and treatment of autoimmune diseases (AD). Their cellular and immunophenotype depend on isolation and culture conditions which may influence their therapeutic application and reflect their in vivo biological functions. We have further characterised the phenotype induced by fibroblast growth factor 2 (FGF2) on healthy donor hBM-MSC focusing on the osteoimmunological markers osteoprotegerin (OPG), receptor activator of nuclear factor kB (RANK), RANK ligand (RANKL) and HLA-DR and their regulation of expression by the inflammatory cytokines IL1β and IFNγ.MethodsRANK, RANKL, OPG and HLA-DR expression in hBM-MSC expanded under specific culture conditions, were measured by RT-PCR and flow cytometry. MAPKs induction by FGF2, IL1β and IFNγ in hBM-MSC was analysed by immunoblotting and RT-PCR.ResultsIn hBM-MSC, OPG expression is constitutive and FGF2 independent. RANKL expression depends on FGF2 and ERK1/2 activation. IL1β and IFNγ activate ERK1/2 but fail to induce RANKL. Only IL1β induces P38MAPK. The previously described HLA-DR induced by FGF2 through ERK1/2 on hBM-MSC, is suppressed by IL1β through inhibition of CIITA transcription. HLA-DR induced by IFNγ is not affected by IL1β in hBM-MSC, but is suppressed in articular chondrocytes and lung fibroblasts.ConclusionsRANKL expression and IL1β regulated MHC-class II, both induced via activation of the ERK1/2 signalling pathway, are specific for progenitor hBM-MSC expanded in the presence of FGF2. HLA-DR regulated by IL1β and ERK1/2 is observed on hBM-MSC during early expansion without FGF2 suggesting previous in vivo acquisition. Stromal progenitor cells with this phenotype could have an osteoimmunological role during bone regeneration.

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“…These patients exhibited fibrosis of the skin (5/5), interstitial pulmonary disease (4/5), vasculopathy (5/5), cardiomyopathy (4/5), and myopathy (2/5). At 18 months of follow-up, 4/5 of the patients improved in skin thickness, in digital ulcers, or in limb necrosis [47]. Limb revascularization was reported in a patient with SS after autologous MSCs-BM infusion [48].…”

Section: Sclerosis Systemic (Ss)mentioning

confidence: 98%

Mesenchymal Stem Cells: Innovative Therapeutic Intervention for Autoimmune Rheumatic Diseases

Meraz¹

2017

HTIJ

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Mesenchymal stem cells (MSCs) are multi-potential non-hematopoietic progenitor cells capable of immuno-modulatory activities that diminish adaptive and innate immune responses. MSCs have been the object of multiple publications because their ability to regulate the immunological system and converted MSCs into a promise of developing cell therapies for various autoimmune rheumatic diseases. The present documents summarize clinical studies with efficacy and satisfactory safety profile in which MSCs have been used for cell therapies in systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis.

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Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: Report of five cases

Cited by 82 publications

References 13 publications

Mesenchymal stromal cells and rheumatic disorders

Mesenchymal stromal cells and rheumatic disorders

FGF2 induces RANKL gene expression as well as IL1β regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells

Mesenchymal Stem Cells: Innovative Therapeutic Intervention for Autoimmune Rheumatic Diseases

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