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Biomanufacturing of Mesenchymal Stromal Cells for Therapeutic Applications

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Cell Culture Engineering and Technology

Part of the book series: Cell Engineering ((CEEN,volume 10))

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Abstract

Mesenchymal Stromal Cells (MSCs) hold great promise to treat a number of diseases either directly, by repairing traumatic tissue injury or damage caused by degenerative diseases, or indirectly through secretion of trophic or immunomodulatory factors. However, it is estimated that 1010–1013 MSCs are needed for a single dose. This, combined with the fact that MSC populations are heterogenous, presents a number of manufacturing challenges. Selection of the appropriate cell culture medium can greatly influence cell metabolism and phenotype, which is important for reducing heterogeneity and batch-to-batch variability. The use of autologous cells vs. allogeneic cells has implications for large scale production and the choice between scale-up or scale-out. Traditional stirred tank bioreactors are better suited for scale-up whereas hollow fiber and packed bed bioreactors may be more appropriate for scale-out strategies. As MSCs are anchorage-dependent, the choice of microcarrier will be important regardless of the bioreactor type and mode of operation. Finally, the clinical success of MSCs is subject to the identification and ability to measure Critical Quality Attributes (CQAs) as a means of determining potency and efficacy. Here we discuss the current state of the cell manufacturing process.

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Abbreviations

AT-MSC :

Adipose tissue derived mesenchymal stromal cell

bFGF :

Basic fibroblast growth factor

BLA :

Biologics License Application

BM-MSC :

Bone marrow derived mesenchymal stromal cell

CMC :

Chemistry, Manufacturing and Controls

CPP :

Critical process parameters

CQA :

Critical quality attribute

DMEM :

Dulbecco’s Modified Eagle Medium

EGF :

Epidermal growth factor

EV :

Extracellular vesicle

FBS :

Fetal Bovine Serum

FDA :

Food and Drug Administration

FGF-2 :

Fibroblast growth factor 2

HGF :

Hepatocyte growth factor

HGF :

Human growth factor

HIF-1 :

Hypoxia-inducible factor 1-alpha

HLA :

Human leukocyte antigen

hMSC :

Human mesenchymal stromal cell

IGF :

Insulin-like growth factor

iMSC :

Induced mesenchymal stromal cell

IND :

Investigational New Drug

iPSC :

Induced pluripotent stem cell

ISCT :

International Society for Cell and Gene Therapy

MSC :

Mesenchymal stromal cell

NSF :

National Science Foundation

PBR :

Packed bed reactor

PDGF :

Platelet-derived growth factor

PLGA :

Poly (lactic-co-glycolic acid)

QbD :

Quality-by-design

TGF-β :

Transforming growth factor beta

UC-MSC :

Umbilic cord derived mesenchymal stromal cell

VEGF :

Vascular endothelial growth factor

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    Ross A. Marklein, Morgan Mantay, Cheryl Gomillion & James N. Warnock

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Marklein, R.A., Mantay, M., Gomillion, C., Warnock, J.N. (2021). Biomanufacturing of Mesenchymal Stromal Cells for Therapeutic Applications. In: Pörtner, R. (eds) Cell Culture Engineering and Technology. Cell Engineering, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-79871-0_9

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