INTRAVENOUS FRESH ALLOGENIC ADIPOSEDERIVED MESENCHYMAL STEM CELLS AFTER STROKE: A PHASE 1A, SAFETY TRIAL (RESSTORE)

ABSTRACT

Background: Despite spontaneous recovery, 60% of stroke patients have residual impairment. Thawed allogenic adipose-derived mesenchymal stem cells (ADSCs) were used in cell therapy studies with promising results. However, fresh allogenic ADSCs, obtained after a short (oneweek) culture from a frozen cell stock, have a better viability and functionality. We assessed feasibility and safety of intravenous (IV) injection of fresh ADSCs in subacute ischemic stroke. Methods: RESSTORE 1a is a first-in-human, open, dose-escalation toxicity 3+3 trial. Four doses of ADSCs were assessed 1, 1.5, 2 or 3 million/ kg injected <10 days after stroke onset. Dose-limiting toxicity (DLT) events were predefined recurrent stroke, myocardial infarction, pulmonary embolism, life-threatening event within one week after treatment. Results: 17 patients were included (mean age +/-SD = 57 +/-18 years;inclusion NIHSS = 14.5 +/-3.5). As 2 patients were not treated (non conformity of ADSC culture and technical problem during infusion), 2 additional patients were included. A DLT event (recurrent minor stroke) occurred in the 2-million/kg group. Among the 15 treated patients, 3 patients received 1, 1.5 or 3 million ADSCs /kg, and 6 patients 2 million ADSCs /kg. A lung carcinoma was diagnosed in an active smoker (1.5 year after treatment) and a patient died after Covid-19 pneumopathy (1 year after treatment). No dose effect on safety was noted. Conclusions: IV injection of fresh allogenic ADSC seems safe in subacute stroke. A multicenter randomized trial is planned.