Filtration methodologies for the clarification and concentration of human mesenchymal stem cells

Cunha, Bárbara; Peixoto, Cristina; Silva, Marta M.; Carrondo, Manuel J.T.; Serra, Margarida; Alves, Paula M.

doi:10.1016/j.memsci.2014.12.041

Cited by 45 publications

(45 citation statements)

References 33 publications

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“…Downstream operations are becoming of significant importance for stem cell bioprocessing, and initial theoretical discussions on separation techniques possibly useful for the cell therapy field as reviewed by Diogo et al [63] are becoming a reality. There is a growing rate of studies on bioprocesses and methods required for the clarification and volume reduction of MSC suspensions using membranes and tangential [64,65] or dead-end [66] filtration. Established techniques in other biotechnological fields are also successfully adopted such as the use of expanded bed chromatography for the washing of MSC suspension resulted in improved efficiency [67].…”

Section: Downstream Bio-processes and Process Integrationmentioning

confidence: 99%

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

Papantoniou¹,

Lambrechts²,

Aerts³

2017

Cell Gene Therapy Insights

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Section: Downstream Bio-processes and Process Integrationmentioning

confidence: 99%

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

Papantoniou¹,

Lambrechts²,

Aerts³

2017

Cell Gene Therapy Insights

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“…For standard biopharmaceutical processes, tangential flow filtration (TFF) [63] is often used for the initial clarification of therapeutic proteins produced in mammalian, bacterial or yeast cell cultures [64]. For the production of ATMPs, TFF processes must be redesigned to meet product quality demands.…”

Section: Cell Separation Clarification and Concentrationmentioning

confidence: 99%

“…For the production of ATMPs, TFF processes must be redesigned to meet product quality demands. The filter material, pore size and initial cell concentration, as well as operating parameters such as shear rate and permeate flux, may influence the recovery of viable, high-quality cells [63]. The impact of shear rate and shear stress on the viability and differentiation potential of hMSCs is well-characterized [65,66].…”

Section: Cell Separation Clarification and Concentrationmentioning

confidence: 99%

“…Further studies are required to optimize the incubation time, taking into account carrier-carrier effects, carrier density and the cell density prior to the harvest [97]. Other groups use the nonmammalian trypsin TrypLE for the detachment of hMSCs [94,[97][98][99][100] on cationic polystyrene charged microcarriers, which achieves high cell quality even in cultures based on SFM [63,100].…”

Section: Cell Detachmentmentioning

confidence: 99%

“…Until recently, the scalable harvesting of hMSCs has received little attention [63,97]. The separation of single cells from the carrier in STR systems can be achieved by dead-end filtration [63,97,100].…”

Section: Separation Clarification and Concentrationmentioning

confidence: 99%

See 2 more Smart Citations

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

Elseberg¹,

Leber²,

Weidner³

et al. 2017

New Insights Into Cell Culture Technology

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In the field of cell therapy, allogenic human mesenchymal stromal cells (hMSCs) are often used in clinical trials, creating a demand for cell mass production using efficient dynamic bioreactor systems. As an advanced therapy medicinal product (ATMP), such cells should meet certain special requirements, including product specifications requiring a production process compatible with good manufacturing practice (GMP). The development of processes in which the cells are the product therefore remains a significant challenge. This chapter describes the requirements at different steps in the upstream and downstream phases of such dynamic processes. Potential solutions are presented and future prospects are discussed, including the selection of media and carriers for the strictly adherent growing cells, allowing efficient cell adhesion and detachment. Strategies for dynamic cultivation in bioreactors are described in detail for fixed-bed and stirred-tank reactors based on GMP requirements and the integration of process analytical technology (PAT). Following cell harvest, separation and purification, the formulation and storage of the product are also described. Finally, the chapter covers important cell quality characteristics necessary for the approval of ATMPs.

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Advances in Lentivirus Purification

Moreira

Cavaco

Faria

et al. 2020

Biotechnology Journal

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Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells. LV production and purification processes have evolved substantially over the last decades. However, the increasing demands for higher quantities with more restrictive purity requirements are stimulating the development of novel materials and strategies to supply the market with LV in a cost-effective manner. A detailed review of each downstream process unit operation is performed, limitations, strengths, and potential outcomes being covered. Currently, the majority of large-scale LV manufacturing processes are still based on adherent cell culture, although it is known that the industry is migrating fast to suspension cultures. Regarding the purification strategy, it consists of batch chromatography and membrane technology. Nevertheless, new solutions are being created to improve the current production schemes and expand its clinical use.

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Filtration methodologies for the clarification and concentration of human mesenchymal stem cells

Cited by 45 publications

References 33 publications

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

Bioprocess engineering strategies for autologous human MSC-based therapies: one size does not fit all

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

Advances in Lentivirus Purification

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