Impact of the type of microcarrier and agitation modes on the expansion performances of mesenchymal stem cells derived from umbilical cord

Loubière, Céline; Sion, Caroline; Isla, Natalia de; Reppel, Loïc; Guédon, Emmanuel; Chevalot, Isabelle; Olmos, Éric

doi:10.1002/btpr.2887

Cited by 20 publications

(30 citation statements)

References 53 publications

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“…For example, Kehoe et al (2012) published harvest efficiency data of 12% for Cytodex-1, whereas we only recovered 1%. Loubière et al (2019) presents similar findings for the expansion of umbilical cord derived wharton’s jelly MSCs, where cells remain attached to Cytodex-1 and Star-Plus and Plastic-Plus are the preferred microcarriers. Plastic-Plus is also preferred in the work of Petry et al (2016) where fold expansions of 16.4 and 13.8 are achieved after 7 and 6 days of culturing human Umbilical Cord MSCs ( Petry et al, 2016 ).…”

Section: Resultssupporting

confidence: 61%

“…The water or PBS from the microcarriers was replaced with pure human platelet lysate (hPL) and placed inside the spinner flasks and in the incubator set at 37°C, 5% CO 2 , and 95% relative humidity. 2 h before the inoculation, the pure hPL was replaced by complete medium (DMEM-C), consisting of DMEM+AA+7.5% hPL ( Loubière et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

“…A clear comparison of the expansion of MSC’s using the different microcarriers Cytodex-1, Star-Plus, Plastic, Plastic-Plus and HillexII is given in Loubière et al (2019) . Here, Star-Plus and Plastic-Plus are chosen as the best microcarriers for the cell culture of MSC’s derived from umbilical cord based on the criteria of cell attachment, expansion and detachment ( Loubière et al, 2019 ). Health authorities are in favor of avoiding the use of animal components due to safety reasons and animal welfare ( Cimino et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium

Beylen

Papantoniou

Aerts

2021

Front. Bioeng. Biotechnol.

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An increasing need toward a more efficient expansion of adherent progenitor cell types arises with the advancements of cell therapy. The use of a dynamic expansion instead of a static planar expansion could be one way to tackle the challenges of expanding adherent cells at a large scale. Microcarriers are often reported as a biomaterial for culturing cells in suspension. However, the type of microcarrier has an effect on the cell expansion. In order to find an efficient expansion process for a specific adherent progenitor cell type, it is important to investigate the effect of the type of microcarrier on the cell expansion. Human periosteum-derived progenitor cells are extensively used in skeletal tissue engineering for the regeneration of bone defects. Therefore, we evaluated the use of different microcarriers on human periosteum-derived progenitor cells. In order to assess the potency, identity and viability of these cells after being cultured in the spinner flasks, this study performed several in vitro and in vivo analyses. The novelty of this work lies in the combination of screening different microcarriers for human periosteum-derived progenitor cells with in vivo assessments of the cells’ potency using the microcarrier that was selected as the most promising one. The results showed that expanding human periosteum-derived progenitor cells in spinner flasks using xeno-free medium and Star-Plus microcarriers, does not affect the potency, identity or viability of the cells. The potency of the cells was assured with an in vivo evaluation, where bone formation was achieved. In summary, this expansion method has the potential to be used for large scale cell expansion with clinical relevance.

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Section: Resultssupporting

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium

Beylen

Papantoniou

Aerts

2021

Front. Bioeng. Biotechnol.

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“…Thus, the detachment efficiency and recovery rate can not be ignored. For example, hMSCs have high expansion fold using Cytodex I microcarriers, but the enzymatic detachment efficiency is low, and it eventually leads to the low cell yield after cell harvest (Weber et al, 2007 ; Sun et al, 2010 ; Schnitzler et al, 2012 ; Timmins et al, 2012 ; Loubière et al, 2019 ). Similarly, although macropores provide more surface area for cell expansion and protect cells from direct flows, i.e., shear stress resulted from the eddies at the Kolmogorov scale, the detachment efficiency is generally not applicable for hMSC expansion (Nienow et al, 2016 ).…”

Section: Bioprocessing For Hmsc Productionmentioning

confidence: 99%

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Tsai

Jeske

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Human mesenchymal stem cells (hMSCs) are a promising candidate in cell therapy as they exhibit multilineage differentiation, homing to the site of injury, and secretion of trophic factors that facilitate tissue healing and/or modulate immune response. As a result, hMSC-derived products have attracted growing interests in preclinical and clinical studies. The development of hMSC culture platforms for large-scale biomanufacturing is necessary to meet the requirements for late-phase clinical trials and future commercialization. Microcarriers in stirred-tank bioreactors have been widely utilized in large-scale expansion of hMSCs for translational applications because of a high surface-to-volume ratio compared to conventional 2D planar culture. However, recent studies have demonstrated that microcarrier-expanded hMSCs differ from dish-or flask-expanded cells in size, morphology, proliferation, viability, surface markers, gene expression, differentiation potential, and secretome profile which may lead to altered therapeutic potency. Therefore, understanding the bioprocessing parameters that influence hMSC therapeutic efficacy is essential for the optimization of microcarrier-based bioreactor system to maximize hMSC quantity without sacrificing quality. In this review, biomanufacturing parameters encountered in planar culture and microcarrier-based bioreactor culture of hMSCs are compared and discussed with specific focus on cell-adhesion surface (e.g., discontinuous surface, underlying curvature, microcarrier stiffness, porosity, surface roughness, coating, and charge) and the dynamic microenvironment in bioreactor culture (e.g., oxygen and nutrients, shear stress, particle collision, and aggregation). The influence of dynamic culture in bioreactors on hMSC properties is also reviewed in order to establish connection between bioprocessing and stem cell function. This review addresses fundamental principles and concepts for future design of biomanufacturing systems for hMSCbased therapy.

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“…Many types of microcarriers have been used in hMSC production in bioreactor systems, including polystyrene, gelatin, dextran and others [23,54]. Evaluations of microcarrier screening for hMSC production have been reported in several studies, primarily regarding three key culture steps: (1) adhesion efficiency, (2) growth rate and cell expansion and (3) ease of detachment [55][56][57]. Rafiq et al systematically evaluated 13 commercial microcarriers for bone marrow-derived hMSC production in bioreactors and determined that Plastic microcarriers were the most optimal [56].…”

Section: Bioprocessing For Microcarrier-based Hmsc Manufacturingmentioning

confidence: 99%

Bioprocessing of Human Mesenchymal Stem Cells: From Planar Culture to Microcarrier-Based Bioreactors

Tsai

Pacak

2021

Bioengineering

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Human mesenchymal stem cells (hMSCs) have demonstrated great potential to be used as therapies for many types of diseases. Due to their immunoprivileged status, allogeneic hMSCs therapies are particularly attractive options and methodologies to improve their scaling and manufacturing are needed. Microcarrier-based bioreactor systems provide higher volumetric hMSC production in automated closed systems than conventional planar cultures. However, more sophisticated bioprocesses are necessary to successfully convert from planar culture to microcarriers. This article summarizes key steps involved in the planar culture to microcarrier hMSC manufacturing scheme, from seed train, inoculation, expansion and harvest. Important bioreactor parameters, such as temperature, pH, dissolved oxygen (DO), mixing, feeding strategies and cell counting techniques, are also discussed.

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Impact of the type of microcarrier and agitation modes on the expansion performances of mesenchymal stem cells derived from umbilical cord

Cited by 20 publications

References 53 publications

Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium

Microcarrier Screening and Evaluation for Dynamic Expansion of Human Periosteum-Derived Progenitor Cells in a Xenogeneic Free Medium

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Bioprocessing of Human Mesenchymal Stem Cells: From Planar Culture to Microcarrier-Based Bioreactors

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