Challenges in Global Access to CAR-T cells: an Asian Perspective.

The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.

Maintenance of Neurogenic Differentiation Potential in Passaged Bone Marrow-Derived Human Mesenchymal Stem Cells Under Simulated Microgravity Conditions.

Human mesenchymal stem cells (hMSCs) are considered to be able to adapt to environmental changes induced by gravity during cell expansion. In this study, we investigated neurogenic differentiation potential of passaged hMSCs under conventional gravity and simulated microgravity conditions. Immunostaining, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), and western blot analysis of neurogenic differentiation markers, neurofilament heavy (NF-H), and microtubule-associated protein 2 (MAP2) revealed that differentiated cells from the cells cultured under simulated microgravity conditions expressed higher neurogenic levels than those from conventional gravity conditions. The levels of NF-H and MAP2 in the cells from simulated microgravity conditions were consistent during passage culture, whereas cells from conventional gravity conditions exhibited a reduction of the neurogenic levels against an increase of their passage number. In growth culture, cells under simulated microgravity conditions showed less apical stress fibers over their nucleus with fewer cells having a polarization of lamin A/C than those under conventional gravity conditions. The ratio of lamin A/C to lamin B expression in the cells under simulated microgravity conditions was constant; however, cells cultured under conventional gravity conditions showed an increase in the lamin ratio during passages. Furthermore, analysis of activating H3K4me3 and repressive H3K27me3 modifications at promoters of neuronal lineage genes indicated that cells passaged under simulated microgravity conditions sustained the methylation during serial cultivation. Nevertheless, the enrichment of H3K27me3 significantly increased in the passaged cells cultured under conventional gravity conditions. These results demonstrated that simulated microgravity-coordinated cytoskeleton-lamin reorganization leads to suppression of histone modification associated with neurogenic differentiation capacity of passaged hMSCs.

Alterations in Nuclear Lamina and the Cytoskeleton of Bone Marrow-Derived Human Mesenchymal Stem Cells Cultured Under Simulated Microgravity Conditions.

Cells sense and respond to environmental changes induced by gravity. Although reactions to conventional culture have been intensively studied, little is known about the cellular reaction to simulated microgravity conditions. Thus, in this study, we investigated the effects of simulated microgravity on human mesenchymal stem cells using a three-dimensional clinostat (Gravite®), a recently developed device used to generate simulated microgravity condition in vitro. Our time-lapse analysis shows that cells cultured under conventional culture conditions have a stretched morphology and undergo unidirectional migration, whereas cells cultured under simulated microgravity conditions undergo multidirectional migration with directional changes of cell movement. Furthermore, cells cultured under conventional culture conditions maintained their spindle shape through fibronectin fibril formation in their bodies and focal adhesion stabilization with enriched stress fibers. However, cells cultured under simulated microgravity conditions were partially contracted and the fibril structures were degraded in the cell bodies. Additionally, paxillin phosphorylation in the cells cultured under simulated microgravity conditions was more intense at the cell periphery in regions near the leading and trailing edges, but was less expressed in the cell bodies compared with that observed in cells cultured under conventional culture conditions. Furthermore, lamin A/C, a major component of the nuclear lamina, was mainly located on the apical side in cells cultured under conventional culture conditions, indicating basal-to-apical polarization. However, cells cultured under simulated microgravity conditions showed lamin A/C localization on both the apical and basal sides. Taken together, these results demonstrate that simulated microgravity-driven fibronectin assembly affects nuclear lamina organization through the spatial reorganization of the cytoskeleton.