Translating Research into Clinical Scale Manufacturing of Mesenchymal Stromal Cells

It sounds simple to obtain sufficient numbers of cells derived from fetal or adult human tissues, isolate and/or expand the stem cells, and then transplant an appropriate number of these cells into the patient at the correct location. However, translating basic research into routine therapies is a complex multistep process which necessitates product regulation. The challenge relates to managing the expected therapeutic benefits with the potential risks and to balance the fast move to clinical trials with time-consuming cautious risk assessment. This paper will focus on the definition of mesenchymal stromal cells (MSCs), and challenges and achievements in the manufacturing process enabling their use in clinical studies. It will allude to different cellular sources, special capacities of MSCs, but also to current regulations, with a special focus on accessory material of human or animal origin, like media supplements. As cellular integrity and purity, formulation and lot release testing of the final product, validation of all procedures, and quality assurance are of utmost necessity, these topics will be addressed

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It sounds simple to obtain sufficient numbers of cells derived from fetal or adult human tissues, isolate and/or expand the stem cells, and then transplant an appropriate number of these cells into the patient at the correct location. However, translating basic research into routine therapies is a complex multistep process which necessitates product regulation. The challenge relates to managing the expected therapeutic benefits with the potential risks and to balance the fast move to clinical trials with timeconsuming cautious risk assessment. This paper will focus on the definition of mesenchymal stromal cells (MSCs), and challenges and achievements in the manufacturing process enabling their use in clinical studies. It will allude to different cellular sources, special capacities of MSCs, but also to current regulations, with a special focus on accessory material of human or animal origin, like media supplements. As cellular integrity and purity, formulation and lot release testing of the final product, validation of all procedures, and quality assurance are of utmost necessity, these topics will be addressed

Validation of an Automated Procedure to Isolate Human Adipose Tissue-Derived Cells by Using the Sepax (R) Technology

The stromal vascular fraction of adipose tissue has gained popularity as a source of autologous progenitor cells for tissue engineering and regenerative medicine applications. The aim of this study was to validate a newly developed, automated procedure to isolate adipose-derived mesenchymal stem/stromal cells (ASCs) from adult human lipoaspirates in a closed and clinical-grade device, based on the Sepax((R)) technology. Using a total of 11 donors, this procedure was compared with the standard operator-based manual separation in terms of isolation yield, clonogenic fraction, phenotype, and differentiation potential of ASCs. As compared with the manual process, automation resulted in a 62% higher isolation yield, with 2.6+/-1.2x10(5) nucleated cells per mL of liposuction, and a 24% higher frequency of clonogenic progenitors. The variability in the isolation yield and clonogenicity across different preparations was reduced by 18% and 50%, respectively. The cytofluorimetric profile and in vitro differentiation capacity into mesenchymal lineages were comparable in the cells isolated using the two procedures. The new Sepax-based process thus allows an efficient isolation of ASCs with higher and more reproducible yields than the standard manual procedure, along with minimal operator intervention. These results are expected to facilitate the use of ASCs for clinical purposes, either within an intraoperative setting or in combination with further in vitro cell expansion/cultivation