Abstract

Human mesenchymal stem cells (hMSCs), also called mesenchymal stromal cells, have been of great interest in regenerative medicine applications because of not only their differentiation potential but also their ability to secrete bioactive factors that can modulate the immune system and promote tissue repair. This potential has initiated many early-phase clinical studies for the treatment of various diseases, disorders, and injuries by using either hMSCs themselves or their secreted products. Currently, hMSCs for clinical use are generated through conventional static adherent cultures in the presence of fetal bovine serum or human-sourced supplements. However, these methods suffer from variable culture conditions (i.e., ill-defined medium components and heterogeneous culture environment) and thus are not ideal procedures to meet the expected future demand of quality-assured hMSCs for human therapeutic use. Optimizing a bioprocess to generate hMSCs or their secreted products (or both) promises to improve the efficacy as well as safety of this stem cell therapy. In this review, current media and methods for hMSC culture are outlined and bioprocess development strategies discussed.

Highlights

  • Human mesenchymal stem cells were first isolated from bone marrow but have since been found in other tissues in the body, such as adipose tissue, umbilical cord blood, the Wharton jelly of the umbilical cord, synovium, lung, pancreas, and muscle [1,2,3]. Whereas these other hMSC sources have emerged in the last few years and are being studied, bone marrow-derived hMSCs (BM-hMSCs) have been rigorously studied over many years and are used in the majority of hMSC clinical studies and trials

  • Chang et al showed that hypoxic preconditioning of Bone marrow-derived human mesenchymal stem cell (BM-hMSC) and transplantation of this conditioned medium (CM) into rats with experimental traumatic brain injury (TBI) resulted in these rats performing significantly better in both motor and cognitive function tests as well as showing increased neurogenesis and decreased brain damage compared with TBI rats transplanted with CM collected from normoxic-expanded BM-MSCs [44]

  • When the CM was incubated with human neural precursor cells for 7 days, the Human neural precursor cell (hNPC) survival was significantly higher in the PPRF-msc6/ bioreactor CM compared with the fetal bovine serum (FBS)/static-expanded CM

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Summary

Introduction

Human mesenchymal stem cells (hMSCs) were first isolated from bone marrow but have since been found in other tissues in the body, such as adipose tissue, umbilical cord blood, the Wharton jelly of the umbilical cord, synovium, lung, pancreas, and muscle [1,2,3]. It is important to develop a bioprocess for the expansion of hMSCs in a well-defined environment, where the nutritional, physiochemical, and mechanical requirements are met, controlled, and maintained (i.e., in bioreactors) for the culture period in order to generate consistent quantities of cells with the same desired properties.

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