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

Papantoniou, Ioannis; Lambrechts, Toon; Aerts, Jean‐Marie

doi:10.18609/cgti.2017.040

Cited by 4 publications

(5 citation statements)

References 45 publications

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“…Efficient expansion of scarce autologous progenitor (MSC) populations is critical for clinical implementation and commercial viability of cell‐based therapeutics . Apart from their high proliferation rate in vitro and their multipotent nature, these cells also have lower regulatory and ethical complications than pluripotent cells, making their transition from bench to bedside relatively easier.…”

Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

Gupta

Hall

Geris

et al. 2019

Stem Cells Translational Medicine

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Xenogeneic‐free media are required for translating advanced therapeutic medicinal products to the clinics. In addition, process efficiency is crucial for ensuring cost efficiency, especially when considering large‐scale production of mesenchymal stem cells (MSCs). Human platelet lysate (HPL) has been increasingly adopted as an alternative for fetal bovine serum (FBS) for MSCs. However, its therapeutic and regenerative potential in vivo is largely unexplored. Herein, we compare the effects of FBS and HPL supplementation for a scalable, microcarrier‐based dynamic expansion of human periosteum‐derived cells (hPDCs) while assessing their bone forming capacity by subcutaneous implantation in small animal model. We observed that HPL resulted in faster cell proliferation with a total fold increase of 5.2 ± 0.61 in comparison to 2.7 ± 02.22‐fold in FBS. Cell viability and trilineage differentiation capability were maintained by HPL, although a suppression of adipogenic differentiation potential was observed. Differences in mRNA expression profiles were also observed between the two on several markers. When implanted, we observed a significant difference between the bone forming capacity of cells expanded in FBS and HPL, with HPL supplementation resulting in almost three times more mineralized tissue within calcium phosphate scaffolds. FBS‐expanded cells resulted in a fibrous tissue structure, whereas HPL resulted in mineralized tissue formation, which can be classified as newly formed bone, verified by μCT and histological analysis. We also observed the presence of blood vessels in our explants. In conclusion, we suggest that replacing FBS with HPL in bioreactor‐based expansion of hPDCs is an optimal solution that increases expansion efficiency along with promoting bone forming capacity of these cells. Stem Cells Translational Medicine 2019;8:810&821

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Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

Gupta

Hall

Geris

et al. 2019

Stem Cells Translational Medicine

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“…The first aim in the collection of meaningful data should be to reduce the signal to noise ratio in the collected data, to make sure that the link between potentially critical process parameters (CPPs) and the product quality is not masked by variability. Reducing variability is discussed more often in literature and the main points to consider are using sensitive readouts, automating the process where possible and applying extreme standardization everywhere else, both on the direct handling of the production process itself as well as the documenting process [8][9][10]. Since most cell-based therapies are originating from research labs, most processes can be made leaner during scale-up, and thereby removing some sources of variability altogether.…”

Section: Streamlining Which Data To Collectmentioning

confidence: 99%

“…While the reduction in process variability and the determination of CPPs and CQAs are process dependent and therefore require a case by case approach [9], the data management and analytical requirements are more similar in nature for all cell and gene therapy manufacturing processes. However, very often manufacturers are still dependent on data management tools that are (partially) paper-based, require a lot of manual user input, involve operator-dependent decisions (e.g.…”

Section: Streamlining Data Col-lection and Managementmentioning

confidence: 99%

Streamlining data management & process analytics for the manufacturing of cell & gene therapies

Bournonville¹,

Lambrechts²,

Pinna³

et al. 2018

Cell Gene Therapy Insights

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“…In the context of patient‐specific ATMP manufacturing (autologous approach), the use of sensor data‐driven automated monitoring and control of the bioreactor become critical because of the inherent patient‐related variability . In that context, a need for change in manufacturing and delivery of stem cell ATMPs has been recognized .…”

Section: Introductionmentioning

confidence: 99%

“…In the context of patient-specific ATMP manufacturing (autologous approach), the use of sensor data-driven automated monitoring and control of the bioreactor become critical because of the inherent patient-related variability. [10][11][12] In that context, a need for change in manufacturing and delivery of stem cell ATMPs has been recognized. [13] Unlike an allogeneic process, in which every run theoretically starts with known, high-quality cells and predictable process behavior, the starting material in an autologous process is highly variable and might come from individuals with compromised health.…”

Section: Introductionmentioning

confidence: 99%

Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture

Bournonville

Lambrechts

Vanhulst

et al. 2019

Biotechnology Journal

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Bioreactors are crucial tools for the manufacturing of living cell‐based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased footprint still need to be reached. In this study, the use of a benchtop bioreactor for in vitro perfusion culture of scaffold‐based tissue engineering constructs is assessed. A low‐footprint benchtop bioreactor system is designed, comprising a single‐use fluidic components and a bioreactor housing. The bioreactor is operated using an in‐house developed program and the culture environment is monitored by specifically designed sensor ports. A gas‐exchange module is incorporated allowing for heat and mass transfers. Titanium‐based scaffolds are seeded with human periosteum‐derived cells and cultured up to 3 weeks. The benchtop bioreactor constructs are compared to benchmark perfusion systems. Live/Dead stainings, DNA quantifications, glucose consumption, and lactate production assays confirm that the constructs cultured in the benchtop bioreactor grew similarly to the benchmark systems. Manual regulation of the system set points enabled efficient alteration of the culture environment in terms of temperature, pH, and dissolved oxygen. This study provides the necessary basis for the development of low‐footprint, automated, benchtop perfusion bioreactors and enables the implementation of active environment control.

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

Cited by 4 publications

References 45 publications

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

Streamlining data management & process analytics for the manufacturing of cell & gene therapies

Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture

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