Investigational product and treatment
The investigational product ProTrans is a clinical-grade cell suspension of MSCs procured from donated Wharton’s jelly tissue and expanded in adherent culture over approximately 4–5 weeks (a maximum of three passages) according to Good Manufacturing Practice (GMP). Umbilical cord tissue donors were provided with both written and oral information regarding tissue donation by the healthcare provider. Informed written consent was provided prior to tissue collection. Expanded cells from five donors were pooled at the point of product formulation prior to cryopreservation. Release characterisation criteria state that the investigational product consists of MSCs expressing (>70%) CD73, CD90, CD105 cell surface antigens and negative (<5%) for CD14, CD19, CD34, CD45 and HLA-DR. This is in line with the International Society for Cell and Gene Therapy’s minimal criteria for MSC identity [The placebo consisted of excipients as above without cell product (5% wt/vol. human serum albumin supplemented with 10% vol./vol. DMSO) and was produced in accordance with procedures and materials used by the manufacturer in the preparation of the investigational product.ProTrans/placebo cryobags cells were thawed bedside in a 37°C water bath. The thawed ProTrans/placebo (5 ml solution) was transferred to a 100 ml saline (154 mmol/l NaCl) infusion bag using a transfer spike. The diluted product was infused at a rate of 5.25 ml/min, equating to 5 million cells/min. Where a dose of 200 million cells or placebo was used, the participant was infused with 210 ml of diluted solution at the same rate as described above (two consecutive infusions of 105 ml). The 25 million cell dose was prepared as described above but the diluted product was infused at a rate of 1.31 ml/min; the infusion was stopped after 20 min resulting in the participant receiving 26.25 ml cell suspension.