Inter-microcarrier transfer and phenotypic stability of stem cell-derived Schwann cells in stirred suspension bioreactor culture

2015 ◽  
Vol 113 (2) ◽  
pp. 393-402 ◽  
Author(s):  
Antos Shakhbazau ◽  
Leila Mirfeizi ◽  
Tylor Walsh ◽  
Holly M. Wobma ◽  
Ranjan Kumar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Schwann Cells ◽  
Bioreactor Culture ◽  
Phenotypic Stability ◽  
Suspension Bioreactor

scholarly journals Core–shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pouria Fattahi ◽  
Ali Rahimian ◽  
Michael Q. Slama ◽  
Kihak Gwon ◽  
Alan M. Gonzalez-Suarez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Scale Up ◽  
Bioreactor Culture ◽  
Stirred Bioreactor ◽  
Cell Spheroids ◽  
Poly Ethylene ◽  
Aqueous Core ◽  
End Stage ◽  
Stirred Bioreactors

AbstractCellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.

scholarly journals Novel low shear 3D bioreactor for high purity mesenchymal stem cell production

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252575
Author(s):  
Andrew B. Burns ◽  
Corinna Doris ◽  
Kevin Vehar ◽  
Vinit Saxena ◽  
Cameron Bardliving ◽  
...  
Keyword(s):  
Cell Culture ◽  
Bone Marrow ◽  
Stem Cell ◽  
High Purity ◽  
Culture Media ◽  
Human Mesenchymal Stem Cells ◽  
Three Dimensions ◽  
Bioreactor Culture ◽  
Differentiation Potential ◽  
Cell Culture Systems

Bone marrow derived human Mesenchymal Stem Cells (hMSCs) are an attractive candidate for regenerative medicine. However, their harvest can be invasive, painful, and expensive, making it difficult to supply the enormous amount of pure hMSCs needed for future allogeneic therapies. Because of this, a robust method of scaled bioreactor culture must be designed to supply the need for high purity, high density hMSC yields. Here we test a scaled down model of a novel bioreactor consisting of an unsubmerged 3D printed Polylactic Acid (PLA) lattice matrix wetted by culture media. The growth matrix is uniform, replicable, and biocompatible, enabling homogenous cell culture in three dimensions. The goal of this study was to prove that hMSCs would culture well in this novel bioreactor design. The system tested resulted in comparable stem cell yields to other cell culture systems using bone marrow derived hMSCs, while maintaining viability (96.54% ±2.82), high purity (>98% expression of combined positive markers), and differentiation potential.

scholarly journals Engineering large cartilage tissues using dynamic bioreactor culture at defined oxygen conditions

2018 ◽  
Vol 9 ◽  
pp. 204173141775371 ◽  
Author(s):  
Andrew C Daly ◽  
Binulal N Sathy ◽  
Daniel J Kelly
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Culture Conditions ◽  
Cartilage Tissue ◽  
Bioreactor Culture ◽  
Dynamic Culture ◽  
Oxygen Conditions ◽  
Static Conditions

Mesenchymal stem cells maintained in appropriate culture conditions are capable of producing robust cartilage tissue. However, gradients in nutrient availability that arise during three-dimensional culture can result in the development of spatially inhomogeneous cartilage tissues with core regions devoid of matrix. Previous attempts at developing dynamic culture systems to overcome these limitations have reported suppression of mesenchymal stem cell chondrogenesis compared to static conditions. We hypothesize that by modulating oxygen availability during bioreactor culture, it is possible to engineer cartilage tissues of scale. The objective of this study was to determine whether dynamic bioreactor culture, at defined oxygen conditions, could facilitate the development of large, spatially homogeneous cartilage tissues using mesenchymal stem cell laden hydrogels. A dynamic culture regime was directly compared to static conditions for its capacity to support chondrogenesis of mesenchymal stem cells in both small and large alginate hydrogels. The influence of external oxygen tension on the response to the dynamic culture conditions was explored by performing the experiment at 20% O2 and 3% O2. At 20% O2, dynamic culture significantly suppressed chondrogenesis in engineered tissues of all sizes. In contrast, at 3% O2 dynamic culture significantly enhanced the distribution and amount of cartilage matrix components (sulphated glycosaminoglycan and collagen II) in larger constructs compared to static conditions. Taken together, these results demonstrate that dynamic culture regimes that provide adequate nutrient availability and a low oxygen environment can be employed to engineer large homogeneous cartilage tissues. Such culture systems could facilitate the scaling up of cartilage tissue engineering strategies towards clinically relevant dimensions.

scholarly journals Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations

Theranostics ◽  
2019 ◽  
Vol 9 (24) ◽  
pp. 7222-7238 ◽  
Author(s):  
Sarkawt Hamad ◽  
Daniel Derichsweiler ◽  
Symeon Papadopoulos ◽  
Filomain Nguemo ◽  
Tomo Šarić ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Bioreactor Cultures ◽  
Induced Pluripotent ◽  
Suspension Bioreactor

scholarly journals Oxygen Transport and Stem Cell Aggregation in Stirred-Suspension Bioreactor Cultures

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102486 ◽  
Author(s):  
Jincheng Wu ◽  
Mahboubeh Rahmati Rostami ◽  
Diana P. Cadavid Olaya ◽  
Emmanuel S. Tzanakakis
Keyword(s):  
Stem Cell ◽  
Oxygen Transport ◽  
Cell Aggregation ◽  
Bioreactor Cultures ◽  
Suspension Bioreactor

scholarly journals Bioreactor Parameters for Microcarrier-Based Human MSC Expansion under Xeno-Free Conditions in a Vertical-Wheel System

2020 ◽  
Vol 7 (3) ◽  
pp. 73 ◽  
Author(s):  
Josephine Lembong ◽  
Robert Kirian ◽  
Joseph D. Takacs ◽  
Timothy R. Olsen ◽  
Lye Theng Lock ◽  
...  
Keyword(s):  
Cost Effective ◽  
Population Doubling ◽  
Bioreactor Culture ◽  
Lot Size ◽  
Fed Batch ◽  
The Media ◽  
Manufacturing Technologies ◽  
Suspension Bioreactor ◽  
Culture Protocol ◽  
Bioreactor Process

Human mesenchymal stem/stromal cells (hMSCs) have been investigated and proven to be a well-tolerated, safe therapy for a variety of indications, as shown by over 900 registered hMSC-based clinical trials. To meet the commercial demand for clinical manufacturing of hMSCs, production requires a scale that can achieve a lot size of ~100B cells, which requires innovative manufacturing technologies such as 3D bioreactors. A robust suspension bioreactor process that can be scaled-up to the relevant scale is therefore crucial. In this study, we developed a fed-batch, microcarrier-based bioreactor process, which enhances media productivity and drives a cost-effective and less labor-intensive hMSC expansion process. We determined parameter settings for various stages of the culture: inoculation, bioreactor culture, and harvest. Addition of a bioreactor feed, using a fed-batch approach, was necessary to replenish the mitogenic factors that were depleted from the media within the first 3 days of culture. Our study resulted in an optimized hMSC culture protocol that consistently achieved hMSC densities between 2 × 105–6 × 105 cells/mL within 5 days with no media exchange, maintaining the final cell population doubling level (PDL) at 16–20. Using multiple hMSC donors, we showed that this process was robust and yielded hMSCs that maintained expansion, phenotypic characteristic, and functional properties. The developed process in a vertical-wheel suspension bioreactor can be scaled to the levels needed to meet commercial demand of hMSCs.

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