Infusion of Allogeneic Stromal Mesenchymal Stem Cells From Wharton´s Jelly in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement to Treatment

Pulmonary Fibrosis, Pulmonary Hypertension, Systemic Sclerosis Pulmonary

refractory systemic sclerosis, systemic sclerosis, pulmonary hypertension, mesenchymal stem cells

Progressive SSc is an entity with limited therapeutic alternatives and a survival rate of less than 45% within the first 3 to 5 years. The disease causes severe limitations in quality of life, ranging from functional impairment to depression. Up to 20% of patients become refractory to conventional treatment with disease-modifying anti-rheumatic drugs (DMARDs) and cyclophosphamide therapy. This condition favors progression to visceral involvement, including gastrointestinal, pulmonary, and pulmonary hypertension manifestations. The latter, considered a poor prognostic factor, increases mortality in this patient population and drastically affects quality of life. For this reason, different therapeutic options have been considered, including cell transplantation and stem cell use. Among the options studied to date are stromal mesenchymal cells derived from Wharton's jelly. These cells have been administered via intravenous infusion or direct application in various disease scenarios, ranging from vascular involvement to interstitial lung disease and pulmonary hypertension, with promising results in terms of clinical progression, quality of life improvement, and prognostic indices. This therapy has demonstrated a favorable safety profile at the time of administration and a low rate of adverse events, with self-limiting fever being the most frequent event. Based on the above and considering the possibility of offering patients without therapeutic alternatives for the disease, in addition to palliative options, an intravenous infusion of stromal mesenchymal stem cells derived from Wharton's jelly is proposed for three patients with progressive SSc refractory to conventional therapy, with pulmonary involvement due to pulmonary hypertension. Under this premise, the research question posed in this study is: What are the effects of the infusion of allogeneic mesenchymal stromal cells derived from Wharton's jelly in patients with systemic sclerosis refractory to conventional treatment with methotrexate or cyclophosphamide, in a population of three patients with severe pulmonary involvement due to pulmonary hypertension?

This study aims to evaluate the therapeutic effects of allogeneic mesenchymal stromal cell infusion as a treatment in patients with systemic sclerosis refractory to conventional therapy. The study population will be selected from the database of families affiliated with Stem Regenerative Medicine according to the inclusion and exclusion criteria and verified by the academic committee. Administration will be performed intravenously, at a concentration of 2 × 10⁶ mesenchymal cells per kilogram of patient body weight. Infusions will be scheduled in conjunction with cyclophosphamide treatment cycles, ten days after each administration within the cyclophosphamide regimen for each patient. To assess safety and therapeutic effects, the occurrence of any adverse event will be documented from the start of infusion until completion of the trial at six months. To evaluate treatment response, assessments will be conducted pre-infusion and at six months post-infusion, including clinical variables, paraclinical parameters, and hemodynamic tests. Skin involvement will be evaluated using the modified Rodnan score, along with assessment of nailfold capillaroscopy, pulmonary function, and structural involvement by high-resolution chest tomography (HRCT), diffusion capacity for carbon monoxide (DLCO), and the 6-minute walk test. As part of cardiovascular assessment, brain natriuretic peptide (BNP) levels and transthoracic echocardiography will be performed. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and SYSQ will be used as assessment tools for pulmonary hypertension. A comparison of these parameters before initiation of therapy and after completion of 24 weeks of the infusion protocol will be conducted.

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