Title of Abstract
Mesenchymal stromal cells (MSCs) from the stromal vascular fraction of adipose tissue have great therapeutic potential. We developed a manufacturing platform and associated regulatory and pre-clinical support for the rapid implementation of internal investigator-initiated clinical trials for a number of diseases. We have manufactured autologous MSC products from more than 134 patients for 6 clinical trials. The products for all of these trials were autologous MSCs derived from adipose tissue that were manufactured using an identical cell culture platform consisting of 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 14) and median adipose biopsy was 0.4 grams (range 0.08 - 5.53, SD 0.89). The median absolute passage 1 cell count was 4.24x106 cells (range 6.5x104 – 4.22x107, SD 8.82x106). We found that the number of cells after passage correlated with adipose biopsy weight (p<0.0001), donor age (p=0.008) and adipose digestion time (p=0.0014), however no correlation was seen with BMI or incubation time before Passage 1. The cells had a median doubling rate of 1.38 per day (range 0.69 - 1.92, SD 0.25). With this protocol, we could routinely generate 500 million cells. Our first time success rate (biopsy to treatment) was 82%, and an overall success rate of 97%. RNA-seq analysis of MSCs from >30 patients revealed remarkable uniformity of the product, compared to the RNA-seq profiles of >200 other human MSCs and stem cell types. Transcriptome analysis reveals that these MSCs have a reproducible cell surface profile of CD markers which have been validated by flow cytometry. In addition to manufacturing data and high-resolution molecular quality control, we will update clinical results on the first four trials to complete enrollment representing more than 80 patients. Overall we have a process where human stromal vascular fraction derived MSCs have been consistently manufactured from adipose tissue independent of age and underlying disease.
Allan B. Dietz and his lab are focused on getting novel therapies to patients. As a Director of the Immune, Progenitor, and Cellular Therapeutics (IMPACT) lab within Mayo's Department of Lab Medicine and Pathology, Dietz focuses on the use of cells as drugs. To that end, the lab is involved in more than 20 investigator initiated clinical trials that have treated more than 500 patients under IND.
Dietz's lab supports these trials through discovery, optimization, validation and manufacturing of the use of cells as drugs. The program also supports our clinical colleagues by managing regulatory submissions, consultation in clinical trial design, and collection of data in support of trial outcomes.
Dendritic cell vaccines
Mesenchymal stem cells
Mesenchymal stem cell/matrix combinations
Allan B. Dietz (1); Andre J. van Wijnen (2); Greg W. Butler (1); Darcie J. Radel (1); Mike Deeds (1); Adam Armstrong (1); Peggy Bulur (1); Sarah Withers (1); Dennis A. Gastineau (1);
All Author Affiliations
Immune, Progenitor, and Cellular Therapeutics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States (1); Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States (2)