Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development

Abstract

Mesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standardized and optimized to guarantee the reproducibility, safety, and efficacy of MSC-based products to be administered to patients. The aim of this study was to develop MSC-based products for use in clinical practice. Quality control assays include cell characterization, cell viability, immunogenicity, and cell differentiation; safety tests such as procoagulant tissue factor (TF), microbiological, mycoplasma, endotoxin, genomic stability, and tumorigenicity tests; and potency tests. The results confirm that the cells express MSC markers; an average cell viability of 96.9%; a low expression of HLA-DR and costimulatory molecules; differentiation potential; a high expression of TF/CD142; an absence of pathogenic microorganisms; negative endotoxins; an absence of chromosomal abnormalities; an absence of genotoxicity and tumorigenicity; and T-lymphocyte proliferation inhibition potential. This study shows the relevance of standardizing the manufacturing process and quality controls to reduce variability due to the heterogeneity between donors. The results might also be useful for the implementation and optimization of new analytical techniques and automated methods to improve safety, which are the major concerns related to MSC-based therapy.

Emerging Landscape of Mesenchymal Stem Cell Senescence Mechanisms and Implications on Therapeutic Strategies

“…Guidelines for cell-based therapies from FDA include requirements for demonstrating the identity, purity, potency, and safety of the product, FDA also emphasizes the need for thorough characterization and consistency of cell products throughout the manufacturing process. EMA guidelines require detailed documentation of the manufacturing process, quality control, and nonclinical and clinical data to ensure the safety and efficacy of the cell product. , Although these regulatory agencies require stringent quality measures to ensure the safety and efficacy of MSCs-based therapies, regulatory guidelines specifically addressing MSCs senescence are still not well-defined. To ensure MSCs-based therapies are safe and effective, collaboration between academic investigators, industry stakeholders and regulatory bodies is urgently needed to develop specific guidelines.…”

Efficacy of adipose‐derived mesenchymal stem cell therapy in the treatment of chronic micro‐ and macrovascular complications of diabetes

“…In addition, MSC-based products also undergo extensive evaluations, including donor screening, purity assays, safety analysis, immunophenotypic characterization and potency measurements, to ensure the reproducibility and quality of the MSC-based products. 24 MSC-based therapy may hold great promise for optimizing glycaemic control in patients with diabetes; however, uncontrolled glycaemic levels may contribute to the ineffectiveness of the therapy in patients with diabetes. 25 Indeed, MSCs have been shown to be more effective in reducing the metabolic hallmarks of diabetes, such as lower requirements for exogenous insulin, and reductions in fasting blood glucose and glycated haemoglobin concentrations, in patients with new-onset diabetes and in patients with overt diabetes, compared with cell transplantation in patients in later stages of the disease.…”