Allogeneic Mesenchymal Stem Cell Therapy for Refractory Lupus Nephritis: Preliminary Results of a Phase I-II Non-RandomizedClinical Trial

Background and Aim: Renal involvement in patients with systemic lupuserythematosus (SLE), known as lupus nephritis (LN), is associated withpoor prognosis. This is mainly due to the fact that a fraction of LN patientsis vulnerable to become resistant to conventional treatments. Pathogenesisof SLE is attributed to autoimmunity and dysregulation of the immunesystem. Hence, immunomodulation is at the top of therapeutic strategiesfor such patients. Mesenchymal stem cells (MSCs) are best known fortheir immunomodulatory effects. This study was designed to evaluate theeffects of allogeneic MSC transplantation on treatment-resistant LN.Methods: In this phase I-II non-controlled clinical trial with before-afterdesign, a series of LN patients (class III and IV) resistant to standardtreatments and having 24 h urine protein > 1 g or urine RBC > 10 or cellularcasts in urine were included. MSCs were extracted from an adipose tissueof patients’ siblings. The patients underwent systemic infusion of 1x106MSCs/kg body weight. After the intervention, the patients were followedup 3 months post-infusion (after), and their disease activity (using SLEDAIscore) and 24-hour urine protein level were compared with those of 3months pre-infusion (before).Results: Nine patients (88.9% female) enrolled in this study with amedian age of 29 (range, 19-37) years. Mean SLEDAI score of patientswas 15.4 ± 5.8 in 3 months pre-treatment which reduced to 6.0 ± 4.8 in3 months post-treatment showing a significant improvement in diseaseactivity (P = 0.014). Nonetheless, the mean values of 24-hour urineprotein excretion, despite a slight reduction after MSC therapy, were notsignificantly different between pre- and post-intervention (2.1 vs. 1.5g/24 h urine, P = 0.308). MSC therapy was found to be safe as excepttransient hypertension in one patient after the infusion, no other acute orchronic adverse effect was observed.Conclusion: Systemic infusion of allogeneic adipose-derived MSCs wassafe and also effective to reduce the disease activity in patients with LNrefractory to conventional treatments. Albeit, this was a preliminary reportand patients should undergo a longitudinal evaluation. Moreover, renalfunction of patients in view of proteinuria did not change significantly,and so, further follow-ups are needed.

کلیدواژه ها:

Systemic Lupus Erythematosus ، Mesenchymal stem cells ، Lupus nephritis