Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media

Abstract

<jats:p>Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.</jats:p>

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

“…Excluded studies (10,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) and reasons are described in Table 4. Most of the included studies described protocols relying on the platelets lyse after freeze-thaw cycles to obtain VBDs.…”

Production of Human Dental Pulp Cells with a Medicinal Manufacturing Approach

“…Cell production under good manufacturing practices procedures implies the use of xeno-free materials and reagents to prevent the risk of viral, bacterial, or prion contamination and the possible induction of immunizing effects in the final recipient (11,22). For this reason, xeno-free dissociating reagents such as TrypLe or Accutase (Life Technologies, Carlsbad, CA) have been recommended for cell passaging instead of the xenogeneic animal trypsin commonly used (23,24).…”

“…In this context, most if not all HDPC culture protocols that have been reported so far are unsatisfactory. Indeed, the use of xeno-or allogeneic cell culture media and long-term cell amplification are known to alter the quality of the final cell-based product (10)(11)(12). These findings make the design of new HDPC isolation, characterization, cryopreservation, and amplification ex vivo procedures that are compliant with good manufacturing practices regarding medicinal products necessary (5,7,13).…”

Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

“…their manufacture is decoupled from delivery to the patient; the cells can be made available on demand. In contrast to autologous therapies, allogeneic products have the potential to be scaled-up, potentially benefitting from the economies of scale experienced by traditional bioprocesses [5,6]. As such, manufacturing technologies employed for allogeneic therapies are likely to differ in terms of nature and scale including the use of traditional scale-up technology such as stirred-tank bioreactors [7,8].…”