BONE MARROW-DERIVED MESENCHYMAL STEM CELL THERAPY IN CHRONIC KIDNEY DISEASE: AN EARLY PHASE CLINICAL TRIAL

• Published in: Cytotherapy (Oxford, England) England), 2024-06, Vol.26 (6), p.S48-S48
• Main Authors: Elhusseiny, K., Alatta, L., Snow, Z.K., Skaff, C., Yin, M., Aslam, N., Porter, I., Mao, M., Trautman, C., Baker, L., Manohar, S., Chebib, F., Lorenz, E., Hickson, L.
• Format: Article
• Language: English
• Subjects: Chronic Kidney Disease; Diabetes; Inflammation
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.083

Chronic kidney disease (CKD) affects over 800 million individuals worldwide and has no cure. However, multiple preclinical studies in CKD animal models show therapeutic potential of mesenchymal stem/stromal cells (MSC). We aimed to investigate MSC safety in a phase I clinical trial and further examined therapy response in individuals with CKD. Allogeneic vertebral bone marrow-derived MSC (®Ossium Health) were intravenously administered via peripheral vein (arm) to CKD participants assigned to one of two dose arms: Arm 1 (n=7) 100 x 10^6 MSCs at Days 0 and 84 and Arm 2 (n=7) 200 x 10^6 MSC at Day 0 only. Study subjects underwent testing at baseline through 6 months (interim review). Kidney function was evaluated by CKD-EPI creatinine equation (estimated glomerular filtration rate; eGFR). Clinical enzyme-linked immunosorbent assay measured serum inflammatory cytokine tumor necrosis factor (TNF)-α. Unpaired t-test was used to compare the means of two independent groups. CKD subjects (n=14) were enrolled with mean age 60.4±11.6 years, 28.6% females, 71.4% white, 36% diabetes mellitus, and baseline eGFR 30.9±7.6 mL/min/1.73m2. No infusion-related or treatment-related serious adverse events were identified. Kidney function remained stable following infusions and over study follow-up, Figure (Left). At 6 months, kidney function was similar to baseline (eGFR 32.1 vs. 30.9 mL/min/1.73m2) with mean eGFR change of 1.2±4.7 mL/min/1.73m2 (all subjects). No difference in 6-month eGFR change was found between dose arm groups (eGFR 1.0±6.5 [Arm 1] vs. 1.4±2.4 [Arm 2], p=0.9). However, proinflammatory marker, TNF-α, had a sustained trend towards lower levels at 3 and 6 months in dose Arm 1 (vs. Arm 2, p=0.09), Figure (Right). Allogeneic bone marrow-derived MSC infusions appear safe and tolerable in CKD participants over short-term follow-up. Interim 6-month studies suggest stable to improved kidney function and a repeat of split-dose MSC administration may yield lower systemic inflammation. Additional, larger-scale and placebo-controlled studies are necessary to examine safety and efficacy of this promising therapeutic.