A potency and toxicology study on tolerability of cryopreserved mesenchymal stem cell product with DMSO in septic mice and nude rats.

Mesenchymal stem/stromal cell (MSC)-based therapies have emerged as a promising treatment for sepsis, supported by encouraging preclinical data. DMSO has been a widely used cryoprotectant in cell-based therapeutic products; however, whether DMSO may cause adverse effects when used for acute critical illness is unclear. This study aimed to assess the impact of DMSO on MSCs and on outcomes in animal models. Cryopreserved MSCs containing 10% DMSO were thawed, washed (Washed MSCs) to remove DMSO, or diluted to 5% DMSO (Diluted MSCs) and evaluated for key quality parameters. Diluted MSCs had significantly higher cell recovery, while viabilities for both MSCs were similar up to 24 h. At 6 h, a higher proportion of early apoptotic cells was observed in Washed MSCs. The potencies of both Washed MSCs and Diluted MSCs were equivalent in rescuing LPS-induced suppression of monocytic phagocytosis. The toxicology study showed that when 5% DMSO-containing MSCs were administered in mice with polymicrobial sepsis, no DMSO-related effects were observed on mortality, body weight loss, body temperature, or organ injury markers. Moreover, no toxicity was detected in nude rats after administration of 5% DMSO-containing MSCs. Altogether, this study demonstrated that cryopreserved MSCs with DMSO did not cause any detectable impairment in animals.