scholarly journals Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Valentin Jossen ◽  
Cedric Schirmer ◽  
Dolman Mostafa Sindi ◽  
Regine Eibl ◽  
Matthias Kraume ◽  
...  
Keyword(s):  
Stem Cells ◽  
Scale Up ◽  
Human Mesenchymal Stem Cells ◽  
Scaling Up ◽  
Pilot Scale ◽  
Culture Broth ◽  
Cell Therapies ◽  
Computational Fluid Dynamics Cfd ◽  
Cell Densities ◽  
Stirred Bioreactors

The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale-up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier-based stirred bioreactors have demonstrated the successful use of Computational Fluid Dynamics (CFD) and suspension criteria (NS1u,NS1) for rapidly scaling up hMSC expansions from mL- to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier-cell-aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth. The dependence of microcarrier-cell-aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d32) versus time. Cultivation at the suspension criteria providedd32values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 106cells mL−1hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterionNS1uwas investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time.

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.

A Scaling-up Approach from Experimental Tunnel to Spray Dryer

2010 ◽  
Vol 6 (1) ◽  
Author(s):  
Xuan-You Li ◽  
Ireneusz Zbicinski ◽  
Jing Wu
Keyword(s):  
Spray Drying ◽  
Scale Up ◽  
Scaling Up ◽  
Pilot Scale ◽  
Drying Kinetics ◽  
Water Evaporation ◽  
Small Scale ◽  
Spray Dryer ◽  
Cfd Modelling ◽  
Initial Water

A scaling-up approach from drying of a thin layer wet material in a experimental tunnel to a pilot scale spray drying was developed through determining drying kinetics of quick evaporation process. Maltodextin was selected as solid material in solution to be dried. Critical moisture contents as a function of initial water evaporation rate (drying rate) shows that there is the same variation between the small scale test tunnel and the pilot scale spray dryer. Result of CFD modelling demonstrates that drying kinetics obtained from the small-scale tunnel could be properly applied to scale-up the spray drying process.

scholarly journals C-STEM: ENGINEERING NICHE-LIKE MICRO-COMPARTMENTS FOR OPTIMAL AND SCALE-INDEPENDENT EXPANSION OF HUMAN PLURIPOTENT STEM CELLS IN BIOREACTORS

2021 ◽  
Author(s):  
Philippe J.R. Cohen ◽  
Elisa Luquet ◽  
Justine Pletenka ◽  
Andrea Leonard ◽  
Elise Warter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Scale Up ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Human Pluripotent Stem Cells ◽  
Cell Therapies ◽  
Cellular Source

Human pluripotent stem cells (hPSCs) have emerged as the most promising cellular source for cell therapies. To overcome scale up limitations of classical 2D culture systems, suspension cultures have been developed to meet the need of large-scale culture in regenerative medicine. Despite constant improvements, current protocols relying on the generation of micro-carriers or cell aggregates only achieve moderate amplification performance. Here, guided by reports showing that hPSCs can self-organize in vitro into cysts reminiscent of the epiblast stage in embryo development, we developed a physio-mimetic approach for hPSC culture. We engineered stem cell niche microenvironments inside microfluidics-assisted core-shell microcapsules. We demonstrate that lumenized three-dimensional colonies maximize viability and expansion rates while maintaining pluripotency. By optimizing capsule size and culture conditions, we scale-up this method to industrial scale stirred tank bioreactors and achieve an unprecedented hPSC amplification rate of 282-fold in 6.5 days.

scholarly journals Hypoxia-Regulated miRNAs in Human Mesenchymal Stem Cells: Exploring the Regulatory Effects in Ischemic Disorders

2019 ◽  
Vol 20 (6) ◽  
pp. 1340
Author(s):  
Carmela Dell’Aversana ◽  
Francesca Cuomo ◽  
Chiara Botti ◽  
Ciro Maione ◽  
Annamaria Carissimo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Autologous Transplantation ◽  
Human Mesenchymal Stem Cells ◽  
Limb Ischemia ◽  
Mirna Expression Profile ◽  
Low Oxygen ◽  
Cell Therapies ◽  
Hypoxic Conditions ◽  
Regulatory Effects

Human mesenchymal/stromal stem cells (hMSC) are the most promising cell source for adult cell therapies in regenerative medicine. Many clinical trials have reported the use of autologous transplantation of hMSCs in several disorders, but with limited results. To exert their potential, hMSCs could exhibit efficient homing and migration toward lesion sites among other effects, but the underlying process is not clear enough. To further increase the knowledge, we studied the co-regulation between hypoxia-regulated genes and miRNAs. To this end, we investigated the miRNA expression profile of healthy hMSCs in low oxygen/nutrient conditions to mimic ischemia and compared with cells of patients suffering from critical limb ischemia (CLI). miRNAs are small, highly conserved, non-coding RNAs, skilled in the control of the target’s expression level in a fine-tuned way. After analyzing the miRNOme in CLI-derived hMSC cells and healthy controls, and intersecting the results with the mRNA expression dataset under hypoxic conditions, we identified two miRNAs potentially relevant to the disease: miR-29b as a pathological marker of the disease and miR-638 as a therapeutic target. This study yielded a deeper understanding of stem cell biology and ischemic disorders, opening new potential treatments in the future.

Scale-up and biomass hold-up characteristics of biological fluidized bed reactors

1994 ◽  
Vol 29 (10-11) ◽  
pp. 353-360 ◽  
Author(s):  
I. Ozturk ◽  
M. Turan ◽  
A. H. Idris
Keyword(s):  
Fluidized Bed ◽  
Scale Up ◽  
Experimental Studies ◽  
Scaling Up ◽  
Pilot Scale ◽  
Fluidized Bed Reactors ◽  
Biofilm Thickness ◽  
Study Results ◽  
Scaling Down ◽  
Comprehensive Study

This paper presents a comprehensive study results on scale-up and biomass hold-up characteristics of biological fluidized bed reactors (BFBR). The overall objective of this study was to establish and test some basic design criteria for the scaling-up or scaling-down of anaerobic fluidized bed reactors. A 12.5 1 laboratory-scale fluidized bed was designed and constructed based on a geometrically similar 70 1 pilot scale fluidized bed and the process performances were compared. Biomass hold up characteristics of the BFBRs were also investigated during the experimental studies. A general expression was developed for predicting the biological fludized bed porosities. Using this expression, both the local and overall fluidized bed porosities could be predicted depending on biofilm thickness, expansion coefficient, media diameter and density. The validity of this expression was tested with the data from this study.

scholarly journals Comparison of Experimental Results to CFD Models for Blending in a Tank Using Dual Opposing Jets

2011 ◽  
Author(s):  
Robert A. Leishear ◽  
Si Y. Lee ◽  
Mark D. Fowley ◽  
Michael R. Poirier ◽  
Timothy J. Steeper
Keyword(s):  
Liquid Radioactive Waste ◽  
Scale Up ◽  
Pilot Scale ◽  
Full Scale ◽  
Experimental Results ◽  
Cfd Models ◽  
Waste Storage ◽  
Scale Models ◽  
Computational Fluid Dynamics Cfd ◽  
Cooling Coils

Research has been completed in a pilot scale, eight foot diameter tank to investigate blending, using a pump with dual opposing jets. The jets re-circulate fluids in the tank to promote blending when fluids are added to the tank. Different jet diameters and different horizontal and vertical orientations of the jets were investigated. In all, eighty five tests were performed both in a tank without internal obstructions and a tank with vertical obstructions similar to a tube bank in a heat exchanger. These obstructions provided scale models of several miles of two inch diameter, serpentine, vertical cooling coils below the liquid surface for a full scale, 1.3 million gallon, liquid radioactive waste storage tank. Two types of tests were performed. One type of test used a tracer fluid, which was homogeneously blended into solution. Data were statistically evaluated to determine blending times for solutions of different density and viscosity, and the blending times were successfully compared to computational fluid dynamics (CFD) models. The other type of test blended solutions of different viscosity. For example, in one test a half tank of water was added to a half tank of a more viscous, concentrated salt solution. In this case, the fluid mechanics of the blending process was noted to significantly change due to stratification of fluids. CFD models for stratification were not investigated. This paper is the fourth in a series of papers resulting from this research (Leishear, et.al. [1–4]), and this paper documents final test results, statistical analysis of the data, a comparison of experimental results to CFD models, and scale-up of the results to a full scale tank.

Bioprocess integration for human mesenchymal stem cells: From up to downstream processing scale-up to cell proteome characterization

2017 ◽  
Vol 248 ◽  
pp. 87-98 ◽  
Author(s):  
Bárbara Cunha ◽  
Tiago Aguiar ◽  
Sofia B. Carvalho ◽  
Marta M. Silva ◽  
Ricardo A. Gomes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Scale Up ◽  
Human Mesenchymal Stem Cells ◽  
Downstream Processing ◽  
Cell Proteome

scholarly journals ESCALONAMENTO DE TECNOLOGIAS: DESENVOLVIMENTO DE PRODUTO E PROCESSO DO LABORATÓRIO À ESCALA PILOTO CONECTADO AO MERCADO (PARTE 1)

Química Nova ◽  
2020 ◽  
Author(s):  
Elimar Vasconcellos ◽  
Priscila Souza ◽  
Marcella Franco ◽  
Vinícius Castro ◽  
Lorena Souza ◽  
...  
Keyword(s):  
Pilot Plant ◽  
Process Development ◽  
Scale Up ◽  
Feasibility Studies ◽  
Basic Research ◽  
Scaling Up ◽  
Pilot Scale ◽  
Economic Feasibility ◽  
One Step ◽  
Expensive Process

TECHNOLOGY SCALE UP: PROCESS DEVELOPMENT FROM THE LABORATORY TO PILOT SCALE CONNECTED TO MARKET (PART 1). In this article, it is described the main aspects to be considered during the process of scaling up hard sciences technologies developed in the Science and Technology Institutes aiming at industrial application. Based on the experience of our group in scaling up, pre-acceleration, and acceleration of different technologies, a methodology was developed and divided into four main stages: Step 1, which involves basic research, Step 2 with a focus on product development, and Step 3 with a focus on process development, all on the laboratory scale and the last one, Step 4 focused on pilot plant development. The most important aspect of this article is to show that many critical questions can be answered even in the laboratory phase. In this way, the risks of Step 4 are minimized. Step 4 is a complicated, lengthy, and expensive process of construction and operation of a pilot plant. Aspects such as proof of concept, technical and economic feasibility studies, minimum viable product, capital expenditures, and operating expenses of pilot plants are approached in a simplified way to serve as a basis for researchers who wants to know the long path to be followed by technology before reaching the industry, consequently the market.

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