Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

Abstract

This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.

Agitation and aeration of stirred-bioreactors for the microcarrier culture of human mesenchymal stem cells and potential implications for large-scale bioprocess development

“…These findings are in line with previously published articles for both microcarrier and monolayer culture [26,27].…”

Low‐Intensity Ultrasound Upregulates the Expression of Cyclin‐D1 and Promotes Cellular Proliferation in Human Mesenchymal Stem Cells

“…Mechanical stimuli such as stretch, strain‐induced oscillatory fluid flow, hydrodynamic stress, and low‐dose ionizing radiation have also been demonstrated to enhance MSC proliferation . Even in dynamic cell culture systems such as spinner flasks and stirred‐tank bioreactors which are used for large‐scale in‐vitro expansion of these cells, the improvement in cell yield were noticed mainly due to increased surface area rather than any improvement in the proliferation capacity of the cells as similar specific growth rates were observed between static and dynamic culture conditions . While activation of either MAPK/ERK pathway, ATP release or Ca 2+ signaling have been implicated in the response of MSCs to mechanical stimuli, the molecular mechanisms that selectively couple the external stimuli to the cellular machinery, which controls MSC proliferation remains poorly understood .…”

“…[7,[10][11][12][13] Even in dynamic cell culture systems such as spinner flasks and stirred-tank bioreactors which are used for large-scale in-vitro expansion of these cells, the improvement in cell yield were noticed mainly due to increased surface area rather than any improvement in the proliferation capacity of the cells as similar specific growth rates were observed between static and dynamic culture conditions. [14][15][16][17] While activation of either MAPK/ERK pathway, ATP release or Ca 2þ signaling have been implicated in the response of MSCs to mechanical stimuli, the molecular mechanisms that selectively couple the external stimuli to the cellular machinery, which controls MSC proliferation remains poorly understood. [7,[10][11][12] This comprehensive knowledge may prove useful in several practical applications, such as in the design of bioreactors for the efficient in vitro expansion of MSCs or treatment strategies that aim to recruit MSCs from in vivo niches to facilitate tissue repair.…”

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

“…The earliest reported study for HPL‐based MSC expansion in a bioreactor system was carried out by Petry et al in 2015 wherein UCB MSCs were expanded using 10% HPL supplemented medium, on microcarriers in spinner flasks . Heathman et al also demonstrated in 2016 that the use of HPL in microcarrier‐based spinner flask culture of BM MSCs resulted in a smaller lag phase and increased yield in comparison to FBS. They further showed that the use of HPL increased interdonor consistency contributing to robust bioprocess outcomes and hence aiding the use of MSCs in clinical settings.…”