Process development and manufacturing approaches for mesenchymal stem cell therapies

Couto, Pedro Silva; Bersenev, Alexey; Rafiq, Qasim A.

doi:10.1016/b978-0-12-816221-7.00002-1

Cited by 11 publications

(3 citation statements)

References 180 publications

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“…The most important challenge for mesenchymal stem cell-based meat is the large-scale production of this cell type to produce mainly muscular fibers for meat production ( 51 ). The mesenchymal stem cells are present in hundreds within the original tissue ( 52 ) and the meat production require tens to hundreds of millions of stem cells ( 53 ).…”

Section: Mesenchymal Stem Cell-based Cultivated Meat Productionmentioning

confidence: 99%

Are genetic drift and stem cell adherence in laboratory culture issues for cultivated meat production?

Jaime-Rodríguez,

Cadena-Hernández,

Rosales-Valencia

et al. 2023

Front. Nutr.

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Mesenchymal stem cell-based cultivated meat is a promising solution to the ecological and ethical problems posed by traditional meat production, since it exhibits a protein content and composition that is more comparable to original meat proteins than any other source of cultivated meat products, including plants, bacteria, and fungi. Nonetheless, the nature and laboratory behavior of mesenchymal stem cells pose two significant challenges for large-scale production: genetic drift and adherent growth in culture. Culture conditions used in the laboratory expose the cells to a selective pressure that causes genetic drift, which may give rise to oncogene activation and the loss of “stemness.” This is why genetic and functional analysis of the cells during culture is required to determine the maximum number of passages within the laboratory where no significant mutations or loss of function are detected. Moreover, the adherent growth of mesenchymal stem cells can be an obstacle for their large-scale production since volume to surface ratio is limited for high volume containers. Multi-tray systems, roller bottles, and microcarriers have been proposed as potential solutions to scale-up the production of adherent cells required for cultivated meat. The most promising solutions for the safety problems and large-scale obstacles for cultivated meat production are the determination of a limit number of passages based on a genetic analysis and the use of microcarriers from edible materials to maximize the volume to surface proportion and decrease the downstream operations needed for cultivated meat production.

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Section: Mesenchymal Stem Cell-based Cultivated Meat Productionmentioning

confidence: 99%

Are genetic drift and stem cell adherence in laboratory culture issues for cultivated meat production?

Jaime-Rodríguez,

Cadena-Hernández,

Rosales-Valencia

et al. 2023

Front. Nutr.

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“…All studies captured in Figure 2 focus on hMSC production with the cell acting as the therapeutic agent (Couto et al, 2020). However, with the increasing interest around exosome production, it is expected that manufacturing processes will be developed specifically optimized with this purpose in mind.…”

Section: Overview Of Hmsc-microcarrier Studies In Stirred-tank Bioreactorsmentioning

confidence: 99%

Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds

Couto

Rotondi

Bersenev

et al. 2020

Biotechnology Advances

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Human mesenchymal stem/stromal cells (hMSCs) present a key therapeutic cellular intervention for use in cell and gene therapy (CGT) applications due to their immunomodulatory properties and multi-differentiation capability. Some of the indications where hMSCs have demonstrated pre-clinical or clinical efficacy to improve outcomes are cartilage repair, acute myocardial infarction, graft versus host disease, Crohn's disease and arthritis. The current engineering challenge is to produce hMSCs at an affordable price and at a commercially-relevant scale whilst minimising process variability and manual, human operations. By employing bioreactors and microcarriers (due to the adherent nature of hMSCs), it is expected that production costs would decrease due to improved process monitoring and control leading to better consistency and process efficiency, and enabling economies of scale. This approach will result in off the shelf (allogeneic) hMSC-based products becoming more accessible and affordable. Importantly, cell quality, including potency, must be maintained during the bioreactor manufacturing process. This review aims to examine the various factors to be considered when developing a hMSC manufacturing process using microcarriers and bioreactors and their potential impact on the final product. As concluding remarks, gaps in the current literature and potential future areas of research are also discussed.

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“…There already exists many reviews exploring the scaling of cell manufacture [151][152][153]. However, the first step for smaller clinical trials typically involves transition to multi-layer cell stacks.…”

Section: Transition To Gmp Manufacturementioning

confidence: 99%

Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products

Childs

Reid

Salmerón‐Sánchez

et al. 2020

Biochemical Journal

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Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.

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Process development and manufacturing approaches for mesenchymal stem cell therapies

Cited by 11 publications

References 180 publications

Are genetic drift and stem cell adherence in laboratory culture issues for cultivated meat production?

Are genetic drift and stem cell adherence in laboratory culture issues for cultivated meat production?

Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds

Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products

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