Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: Promises, problems and prospects

Abstract

Mesenchymal stem cells (MSCs) are one of the few stem cell types used in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair, due to their unique paracrine capacity, multiple differentiation potential, active components in exosomes, and effective mitochondria donation. At present, MSCs derived from tissues such as bone marrow and umbilical cord are widely applied in preclinical and clinical studies. Nevertheless, there remain challenges to the maintenance of consistently good quality MSCs derived from different donors or tissues, directly impacting their application as advanced therapy products. In this review, we discuss the promises, problems, and prospects associated with translation of MSC research into a pharmaceutical product. We review the hurdles encountered in translation of MSCs and MSC–exosomes from the research bench to an advanced therapy product compliant with good manufacturing practice (GMP). These difficulties include how to set up GMP‐compliant protocols, what factors affect raw material selection, cell expansion to product formulation, establishment of quality control (QC) parameters, and quality assurance to comply with GMP standards. To avoid human error and reduce the risk of contamination, an automatic, closed system that allows real‐time monitoring of QC should be considered. We also highlight potential advantages of pluripotent stem cells as an alternative source for MSC and exosomes generation and manufacture.

Anti-stroke biologics: from recombinant proteins to stem cells and organoids

“…52 In addition, specialised stem cell banks exist to collect, preserve and distribute various stem cell types for research, medical and therapeutic purposes, adhering to ethical and regulatory standards. 53 The availability of stem cells is influenced by sourcing methods, ethical considerations and regulatory frameworks, with ongoing technological advancements continually refining the collection, storage and application processes for enhanced prospects in medical research and treatment. 53 Enhanced endogenous neurogenesis and angiogenesis poststroke have been shown to significantly enhance neurofunctional recovery; our related work on NAMPT also had similarly substantiated this claim.…”

“…53 The availability of stem cells is influenced by sourcing methods, ethical considerations and regulatory frameworks, with ongoing technological advancements continually refining the collection, storage and application processes for enhanced prospects in medical research and treatment. 53 Enhanced endogenous neurogenesis and angiogenesis poststroke have been shown to significantly enhance neurofunctional recovery; our related work on NAMPT also had similarly substantiated this claim. 1 54-56 Numerous preclinical trials have demonstrated that stem cell transplantation after stroke can improve neurogenesis, synaptogenesis and angiogenesis in the brain, leading to functional recovery.…”

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

“…The generation, surface protein expression and content composition of sEVs are influenced by cell development conditions and the culture medium formulation. 130 Maintaining consistent cell growth ensures extracellular vesicle stability, uniformity, and efficacy. Furthermore, it should be noted that storage conditions might influence the size distribution of sEVs and the stability and biodistribution of cells.…”

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

“…MSCs are attractive cell sources in regenerative medicine based on their abilities to self-renew and differentiate into mesenchymal tissue lineage [137]. During the last few years, the use of MSCs and their cell-free derivatives has seen an increasing number of applications in disparate medical fields, including chronic musculoskeletal conditions [138][139][140][141][142]. All of these approaches would require cell harvesting and transplantation.…”