Processing and Ex Vivo Expansion of Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells for the Development of an Advanced Therapy Medicinal Product for use in Humans

Abstract

Adipose tissue (AT) represents a commonly used source of mesenchymal stem/stromal cells (MSCs) whose proregenerative potential has been widely investigated in multiple clinical trials worldwide. However, the standardization of the manufacturing process of MSC-based cell therapy medicinal products in compliance with the requirements of the local authorities is obligatory and will allow us to obtain the necessary permits for product administration according to its intended use. Within the research phase (RD), we optimized the protocols used for the processing and ex vivo expansion of AT-derived MSCs (AT-MSCs) for the development of an Advanced Therapy Medicinal Product (ATMP) for use in humans. Critical process parameters (including, e.g., the concentration of enzyme used for AT digestion, cell culture conditions) were identified and examined to ensure the high quality of the final product containing AT-MSCs. We confirmed the identity of isolated AT-MSCs as MSCs and their trilineage differentiation potential according to the International Society for Cellular Therapy (ISCT) recommendations. Based on the conducted experiments, in-process quality control (QC) parameters and acceptance criteria were defined for the manufacturing of hospital exemption ATMP (HE-ATMP). Finally, we conducted a validation of the manufacturing process in a GMP facility. In the current study, we presented a process approach leading to the optimization of processing and the ex vivo expansion of AT-MSCs for the development of ATMP for use in humans.

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

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Clinical Prospect of Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles in Kidney Disease: Challenges and the Way Forward

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Application of Elevated Atmospheric Pressure and Hypoxia Enhance Pluripotency and Stem Cell Differentiation

“…To date, few if any studies demonstrate the role of atmospheric pressure on pluripotent stem cell generation and differentiation, however its positive influence on adult stem cell differentiation has been reported. For example, chondrogenic and osteogenic differentiation of mesenchymal stem cells is shown to be positively regulated by elevated atmospheric pressure (Labedz-Maslowska, 2021;Zhou et al, 2014;Wagner et al, 2008) and there is a recognized need for the ability to produce functional HSPCs ex vivo for clinical use and pressure could be one of factors to achieve this (Li et al, 2021). Translating these regulatory effects of atmospheric pressure to iPSCs, which have virtually limitless differentiation potential, could enable more efficient generation of lineage-specific cell types.…”