A manufacturing platform for adipose derived mesenchymal stromal cells (AdMSC) supporting clinical trials for diverse indications

Mesenchymal stromal cells have great potential as a therapy for a variety of diseases. We developed a manufacturing platform and the associated regulatory and pre-clinical support for the rapid implementation of internal investigator-initiated clinical trials for a number of diseases. Between July 2012 and Oct 2014, we manufactured 64 AdMSC products from 60 patients for 5 clinical trials. The disease indications include Amyotrophic Lateral Sclerosis, Multiple System Atrophy, Atherosclerotic Renal Artery Stenosis, Fistulizing Crohn’s Disease, and Ovarian Cancer. Aside from trial specific administration practices, the products for all of these trials were manufactured on an identical platform consisting of AdMSCs expanded in Advanced MEM (Gibco Life Technologies, Grand Island, NY) supplemented with human platelet lysate (PLTMax, Mill Creek LifeSciences, Rochester MN). The median age of these patients was 58 years old (range 18 - 80, SD 12) and median adipose biopsy was 0.3 grams (range 0.1 - 5.5, SD 1.0). The dose of MSCs varied for each patient and within each study, but using the calculated median population doublings, this platform could consistently produce >500x106 cells in 16.5 days. These products had a median doubling rate per day of 1.45 (range 0.97 - 1.92, SD 0.22). We have found no correlation in the doubling times with age or BMI. Some patients received products that were administered immediately post thaw, while others were given after a four day recovery period in culture. The median doubling rate per day of MSCs allowed to recover in culture was 0.72 (range 0.13 - 0.95, SD 0.19). Sixty products were administered to 44 patients with no acute significant adverse events. Overall we have demonstrated that MSCs can be consistently manufactured from adipose tissue across a range of ages and disease groups.