Addressing the Manufacturing Challenges of Cell-Based Therapies

Microbial–stem cell interactions in periodontal disease

“…Culture-expanded MSCs have been successfully used in regenerative medicine in combination with biomaterials for the regeneration of oral and maxillofacial bone deficiencies [45][46][47][48]. Despite these promising clinical results, the use of autologous MSCs has some major limitations such as regulatory constraints, costs for amplification and quality controls, logistics of transportation, and surgical appliance of fresh cells and patient-to-patient variability in the cell expansion efficiency and regenerative outcome [49][50][51]. Finally, the exact mechanism of regeneration by MSCs remains partially unknown, particularly when there is microbial challenge at the site of operation as in the paradigm of periodontitis, where microorganisms within the periodontal pockets are in a constant interplay with the resident host cells.…”

Critical Analysis of cGMP Large-Scale Expansion Process in Bioreactors of Human Induced Pluripotent Stem Cells in the Framework of Quality by Design

“…Downstream processing is a fundamental step in cell manufacturing, as the concentration of the product is typically high and suboptimal conditions at this stage can have a substantial effect on the final product [ 91 ]. Following expansion, cells need to be harvested, concentrated, washed to discard unwanted contaminants, formulated in a cryopreservation buffer, transferred into containers, and stored in liquid nitrogen vapor [ 91 , 92 ].…”

“…Tangential flow filtration (TFF) and continuous counterflow centrifugation allow for simultaneous washing and volume reduction steps in a closed system [ 36 , 91 , 92 ]. In TFF, cells are recirculated along membranes, while fluid pressure removes the spent media through filtration.…”

“…Downstream processing is a fundamental step in cell manufacturing, as the concentration of the product is typically high and suboptimal conditions at this stage can have a substantial effect on the final product [91]. Following expansion, cells need to be harvested, concentrated, washed to discard unwanted contaminants, formulated in a cryopreservation buffer, transferred into containers, and stored in liquid nitrogen vapor [91,92]. With regards to the harvest strategy, hiPSCs suffer during single-cell enzymatic dissociation and endure passaging as small clumps (5-20 cells) much better by enzyme-free methods, that is, ethylenediamine tetraacetic acid (EDTA) in phosphate-buffered saline [60,93].…”

Evidence for the existence of CD34+ angiogenic stem cells in human first‐trimester decidua and their therapeutic for ischaemic heart disease

“…4,5 However, the effectiveness of some clinical trials is still controversial. 6,7 Therefore, the purpose of this research was to identify new stem cells that have strong angiogenic ability and low immunogenicity that could function as optimal seed cells for treating IHD.…”