Abstract
Dimethyl sulfoxide (DMSO) is the preferred cryoprotectant for the cryopreservation of mesenchymal stromal cells (MSCs). As DMSO has been associated with in-vivo toxicity, its potential side effects when administered with MSC therapies are a matter of debate. To contribute to the assessment of the potential patient safety risk that may be posed by typical amounts of DMSO delivered with cryopreserved MSC-based therapy products, published safety data from intravenous and topical applications of DMSO and DMSO-containing MSC products in humans were reviewed. For the intravenous route, 1173 patients treated with 1-24 DMSO-containing MSC infusions were analyzed. For the topical route, for which data from the administration of DMSO-containing MSC products are lacking, the risk of local toxicity was estimated on the basis of the available information from the topical use of DMSO for wound healing purposes, whereas the risk of systemic toxicity was estimated on the basis of a worst-case scenario assuming 100% transdermal absorption. The doses of DMSO delivered via intravenous administration of MSC products were 2.5-30 times lower than the dose of 1 g DMSO/kg typically accepted for hematopoietic stem cell transplantation, and with adequate premedication, only isolated infusion-related reactions, if any, were reported. Published experience with the application of DMSO to skin wounds suggests that DMSO concentrations applied with undiluted DMSO-cryopreserved MSC products are unlikely to cause significant local adverse effects. In the worst-case scenario, assuming complete systemic absorption of DMSO from an MSC product applied to a large wound in a lightweight patient, the systemic exposure to DMSO would be approximately 55 times lower than that from an intravenous dose of 1 g/kg. In conclusion, the available data do not indicate significant safety concerns with the DMSO contained in intravenous or topical MSC products cryopreserved according to current standard protocols.