Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19

Abstract

Adipose-derived stem cells (ADSCs) have raised big interest in therapeutic applications in regenerative medicine and appear to fulfill the criteria for a successful cell therapy. Their low immunogenicity and their ability to self-renew, to differentiate into different tissue-specific progenitors, to migrate into damaged sites, and to act through autocrine and paracrine pathways have been altogether testified as the main mechanisms whereby cell repair and regeneration occur. The absence of standardization protocols in cell management within laboratories or facilities added to the new technologies improved at patient’s bedside and the discrepancies in cell outcomes and engraftment increase the limitations on their widespread use by balancing their real benefit versus the patient safety and security. Also, comparisons across pooled patients are particularly difficult in the fact that multiple medical devices are used and there is absence of harmonized assessment assays despite meeting regulations agencies and efficient GMP protocols. Moreover, the emergence of the COVID-19 breakdown added to the complexity of implementing standardization. Cell- and tissue-based therapies are completely dependent on the biological manifestations and parameters associated to and induced by this virus where the scope is still unknown. The initial flow chart identified for stem cell therapies should be reformulated and updated to overcome patient infection and avoid significant variability, thus enabling more patient safety and therapeutic efficiency. The aim of this work is to highlight the major guidelines and differences in ADSC processing meeting the current good manufacturing practices (cGMP) and the cellular therapy-related policies. Specific insights on standardization of ADSCs proceeding at different check points are also presented as a setup for the cord blood and bone marrow.

MIT-001 Restores Human Placenta-Derived Mesenchymal Stem Cells by Enhancing Mitochondrial Quiescence and Cytoskeletal Organization

“…Forni et al also reported up-regulated mitochondrial fusion during the adipogenic or osteogenic differentiation of MSCs, while chondrogenic differentiation requires increased expression of mitochondrial fission-related genes [ 37 ]. Given that most studies demonstrated only the inverse proportion of mitochondrial fission and fusion, the simultaneous increase and decrease in DRP1 and MFN1/2 under TNF-α/IFN-γ exposure provides a new perspective on the more systemic landscape of mitochondrial dynamics in impaired stem cells and requires more detailed research [ 32 , 37 , 38 , 39 ].…”

“…Mitochondrial distribution can also be considered a crucial marker for MSC differentiation [ 38 ]. Quinn et al reported that undifferentiated MSCs exhibit a perinuclear arrangement of the mitochondria around the nucleus and are uniformly distributed in the cytoplasm [ 40 ].…”

Novel cell-based therapies in inflammatory bowel diseases: the established concept, promising results

“…The long-term safety and efficacy of both autologous and allogeneic MSCs have since been evaluated in IBDs treatment. Autologous administration of MSCs was used in several human studies [ 76 – 80 ]. Local injection of autologous BM-MSCs in patients with perianal fistula was safe, well tolerated and following resolution of inflammation, decreased CD activity index (CDAI) score and induced mucosal healing in patients [ 81 ].…”

Single-Use Bioreactors for Human Pluripotent and Adult Stem Cells: Towards Regenerative Medicine Applications

“…These bioreactors were developed to be single use and are available in various scales, from 100 mL to 80 L (MagDrive) or from 3 L to 500 L (AirDrive), and feature an embedded automatic controller starting from the 3 L units ( Figure 8 ). The characterisation of VWBRs is so far limited, and therefore, no empirical correlations for bioreactor scale-up are yet available, but reports of computational fluid dynamics-based hydrodynamic modelling have already been published [ 66 , 114 ].…”

“…The same group then optimised the culture protocol, in terms of inoculation (pre-formed aggregates vs. single cell), agitation speed and harvesting enzyme, and exposure time. With the optimised conditions, a maximum of (6.5 ± 0.6) × 10 8 cells could be obtained, which could be passaged to 500 mL volume vessels [ 66 ]. In all cases, the expression of pluripotency markers and differentiation potential of the cells were found to be maintained.…”