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Mesenchymal stromal cells (MSC) are multipotent cells which carry immunomodulatory, pro-angiogenic and anti-fibrotic properties, that can target Systemic Sclerosis (SSc) pathogenesis and its clinical manifestations. The increasing use of MSC, harvested from bone marrow (MSC(M)), adipose tissue (MSC(AT)), or umbilical cord (MSC(UC)) in a variety of indications, provides consistent evidence supporting their safety in humans. The efficacy of MSC(M) intravenous (IV) injection for treating acute graft versus host disease led to their marketing approval in 2012 and MSC(AT) (Alofisel) were approved for severe Crohn's fistula in 2018.
MSC represent a promising therapeutic approach for SSc. We previously a) showed disease-specific abnormalities in MSC(M) from SSc patients, providing strong rationale to use allogeneic MSC to treat SSc patients, b) completed the first phase I/II dose escalation trial using allogenic MSC(M) infusion in 20 severe SSc patients (ClinicalTrials.gov: NCT02213705, PHRC AOM 11-250) with no safety issues, significant improvement in skin fibrosis at 3 to 6 months after infusion which appeared lower thereafter, thereby supporting the need for repeated infusions.
In vitro, experimental and clinical studies suggest that MSC properties vary according to their tissue of origin/source. We demonstrated that compared to MSC(M), MSC(AT) are easier to harvest and display higher proliferative capability before entering senescence, higher genetic stability, and superior immunosuppressive properties.
The objective of the present research is the successful production of allogeneic MSC(AT) derived from selected healthy donors, with adequate phenotypic criteria according to the International Society for Cell & Gene Therapy.
Considering the above rationale, these MSC(AT) will subsequently be used in a Phase I/II randomized clinical trial testing allogeneic MSC(AT) systemic infusion for treatment of severe systemic sclerosis.
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Weight < 50 kg
Positive viral serology : Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Hepatitis E Virus (HEV), syphilis, Human T Lymphotropic virus (HTLV), active infection with IgM+ for toxoplasmosis, Epsiten Barr Virus (EBV), Cytomegalovirus (CMV)
Active generalized infection (viral, parasitic, tuberculosis, leprosy...)
Significant comorbidities according to donor health history or existing risk factors for viral infections within the past 12 months:
Uncontrolled hypertension
Human dura mater transplant
Surgical history of the central nervous system
Dementia or neurological disease that may evoke subacute spongiform encephalopathy
Family history as part of subacute spongiform encephalopathy
Hematological malignancies
Active or any past history of cancer
History of chemotherapy or irradiation
Systemic or autoimmune disease
Multiple adenopathy, splenomegaly, hepatomegaly
Icterus
Haemophilia
Known insulin-dependent diabetes
Treatment with extractive pituitary hormones (including growth hormones)
Steroids therapy (for more than 5 days) in the past 3 months
Lithium treatment
Pregnancy
Deprived of freedom
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Interventional model
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6 participants in 1 patient group
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Central trial contact
Dominique Farge, Pr; Jérôme Lambert, Dr
Data sourced from clinicaltrials.gov
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