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GMP info
Regarding suitability of Eppendorf bioprocess equipment in GMP-regulated applications, please reach out to your Eppendorf sales representative.
Stem Cell Bioprocessing
Bioreactors for stem cells
Stem cell process development
Stem cell process transfer from R&D to production
Eppendorf bioreactors for stem cells
Customer success stories
Stem cells are unique in that they possess the capacity for self-renewal and to develop into various cell types. This ability makes them extremely useful for biotechnological applications such as cell therapy , drug discovery, and the creation of modern food . Research and development in these application areas require large numbers of high-quality cells. However, establishing and growing highly sensitive cell cultures outside of their natural physiological environment is a labor and time intensive process. It is essential that the ideal conditions for cell growth can be produced and controlled, and that this system is scalable to generate the large quantity of cells required for cellular applications.
Stirred-tank bioreactors facilitate the efficient expansion of stem cells through their scalable design, the ability to tightly control key parameters, and automation. Learn more about bioreactors for stem cells and how to get started with stem cell bioprocessing.
Stirred-tank bioreactors facilitate the efficient expansion of stem cells through their scalable design, the ability to tightly control key parameters, and automation. Learn more about bioreactors for stem cells and how to get started with stem cell bioprocessing.
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Bioreactors for stem cells
What are bioreactors?
The success of stem cell bioprocessing relies on robust and reproducible culture conditions and processes. Bioreactors are vessels used to culture a broad range of cell types in precisely controlled conditions to provide optimal productivity, efficiency, and product quality. Bioreactors come in a range of sizes from milliliters to hundreds of liters. They can either be single-use or made of glass or stainless steel.
For more information, check out our introduction to bioprocessing, where we ask – what is a bioreactor?
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What are the benefits of bioreactors for stem cell cultivation?
Although widely used in stem cell research and production due to their ease of use and affordability, cell culture flasks are limited in terms of control and scalability. Bioreactors offer many benefits, such as:
- Better reproducibility: In bioreactors you can monitor critical culture parameters including pH , Dissolved Oxygen (DO) , temperature and nutrient feeding and automatically adjust them by bioprocess monitoring and control software. Like this, culture conditions and as a result culture outcome can be better reproduced.
- Simpler scale-up: Many stem cell applications in cell therapy development, drug discovery, and lab-grown meat require high cell numbers. When using a bioreactor one can increase the size of the culture vessel to many liters and even more, unlike cell culture flasks where the number of vessels must be increased after a certain point. Using one big vessel instead of many small ones saves space and manual labor, thus simplifying the process of increasing the number of cultured cells.
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Gain a more thorough understanding of the benefits of using a bioreactor with our white paper .
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How to use bioreactors for stem cell expansion?
The majority of stem cells are adherent cells and require a support matrix to grow. In 2D cultures, this means growing stem cells in dishes or flasks, however, these systems are often challenging to scale-up. Fortunately, there are many available options to grow adherent cells in bioreactors including:
- Cell-only aggregates: This technique involves allowing cells to adhere to one another and form an aggregate. This technique is often used for the cultivation of induced pluripotent stem cells (iPSCs) in bioreactors.
- Microcarriers: Microcarriers are spherical beads, which are added to the culture medium and serve as a surface for adherent cells such as mesenchymal stem cells (MSCs) to attach and grow. Microcarriers are made of a variety of materials. They can have specific coatings to enhance cell attachment, yield and viability.
- Fibra-Cel® Disks: Disks made of polyester and polypropylene provide a growth support for adherent cells in both packed-bed bioreactors and in suspension. Due to their three-dimensionality and fibrous material, Fibra-Cel Disks allow for easy cell attachment, a high surface-to-volume-ratio, and provide a low-shear environment. This often results in increased total biomass compared to many microcarriers.
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Discover the advantages of different matrix systems for adherent cells in our white paper .
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How to use bioreactors for stem cell differentiation?
Efficient differentiation of stem cells into the desired cell type is critical for cell therapy applications, disease modeling, and the production of cultured meat. Stem cell differentiation is influenced by the culture conditions, such as the medium composition, physiochemical environment, cell-cell and cell-matrix interactions, and more. Bioreactors are an excellent platform that allow you to control, optimize, and reproduce the precise conditions required for specific cell differentiation. Stem cells have been successfully cultured and differentiated into different cell types using Eppendorf bioreactors. Please have a look at the documents below for some examples:
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PDF 6 MB
Application Note
PDF 1.9 MB
Application Note
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Case Study
PDF 0.9 MB
Application Note
How can I switch from stem cell culture in flasks and dishes to bioreactors?
The first step in optimizing your stem cell bioprocess is to switch from 2D to 3D processes for improved scalability and control. Here we offer some tips and tricks for process transfer to bioreactors and share the experiences of experts.
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Infographic: Stem cell culture in bioreactors
Download our infographic for some tips to help you transfer your stem cell culture from dishes and flasks to bioreactors.
Interview: Increasing hiPSC yields
Robert Zweigerdt fromHannover Medical Schoolexplains how his groupconverted stem cell culture to bioreactors and which process optimization measures were crucial to increase the cell yield.
Panel discussion: Preparing your stem cell cultivation for commercialization
At what point in yourdevelopment should youconsider which cultivation method? How to switch from static to stirred-tank cultivation? Listen to experts from the Cell and Gene Therapy Catapult and Eppendorf to discover answers to these and more questions.
How to culture mesenchymal stem cells in bioreactors?
MSCs are multipotent cells derived from the bone marrow, adipose tissue, cord blood or other tissues related to the embryonic mesoderm. MSCs hold great potential for both cell-based therapies and for the creation of novel food. However, both of these industrial applications require robust manufacturing processes to increase the consistency and scalability of MSC production. MSCs are often grown in stirred-tank bioreactors utilizing microcarriers.
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Read our application notes for some guidelines on how to culture MSCs in bioreactors
PDF 8 MB
A straightforward workflow to help users to culture mesenchymal stem cells in bioreactors
PDF 0.9 MB
MSCs were cultured on microcarriers and retained their potential to differentiate into osteocytes and chondrocytes
How to culture iPSCs in bioreactors?
Robust large-scale hiPSC production is required to fulfill the large cell quantities needed in cell therapy development. Bioreactors provide a controllable culture environment and offer a scalable platform for culturing pluripotent stem cells. iPSCs are often grown as cell aggregates in stirred-tank bioreactors.
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Read our application notes for some guidelines on how to culture hiPSCs in bioreactors
PDF 3 MB
This application note provides an example of iPSC culture in the SciVario twin bioreactor system
PDF 5 MB
Demonstrates the power of process control in bioreactors
Stem cell process development
How can I establish a robust, reproducible stem cell bioprocess?
How to monitor and control a bioprocess
To obtain robust processes and cells of consistent, high quality it is indispensable to understand, which process parameters influence the cells’ characteristics. Learn more about bioprocess monitoring and control here and understand, how the integration of sensors and control software into bioreactors enables real-time monitoring to gain a better understanding of the process and to automate process control.
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How to develop a bioprocess
Identifying critical process parameters, automating routine tasks, and scaling up bioprocesses are integral parts of bioprocess development. Learn more about bioprocess development here!
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How can I increase the yield of my stem cell culture in bioreactors?
Increasing cell density is a vital component of research in stem cell bioprocessing. Bioreactors are suitable tools, as they allow for monitoring and controlling the cell growth environment. Furthermore, they facilitate nutrient addition and waste product removal. One important consideration when optimizing your stem cell bioprocess is therefore to consider which operation mode is most suitable for your cells. A number of techniques exist including batch, fed-batch, continuous, and perfusion cultures and each has its own benefits and drawbacks.
Find out, how the group of Robert Zweigerdt at MH Hannover increased hiPSC yield tenfold to 35 million hiPSCs per mL by optimizing process parameters and feeding strategy.
Find out, how the group of Robert Zweigerdt at MH Hannover increased hiPSC yield tenfold to 35 million hiPSCs per mL by optimizing process parameters and feeding strategy.
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How to produce stem cell-derived exosomes in bioreactors?
Stem cell-derived exosomes are currently of great interest as cell-free therapeutic tools due to their strong diagnostic and therapeutical potential in various diseases models. To explore the use of exosomes in preclinical research, large amounts need to be produced.
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Stem cell process transfer from R&D to production
What bioprocess equipment does Eppendorf offer for stem cell manufacturing?
Eppendorf offers a suite of products that together support compliance of bioprocess applications with GMP requirements. This includes bioprocess controllers and bioreactors which can be qualified for use in regulated environments, bioprocess SCADA software that is 21 CFR Part 11 and EudraLex Volume 4 Annex 11 compatible, and services to support your compliance to GMP requirements.
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Where can I find more information about the role of stirred-tank bioreactors in stem cell manufacturing?
- Watch webinar : Join experts from Hannover Medical School, Pluri Inc., and Eppendorf and find out more about unleashing the power of stirred-tank bioreactors for cell and gene therapies!
- Access the recording of scientifc talks from our last Stem Cell Community Day to get expert insights into stem cell process development, scale-up, and manufacturing.
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Stem cell expertise at Eppendorf
Eppendorf has a long, established history working with stem cell processes in 3D cultures. Since 2012, Eppendorf bioreactor systems have been used to grow stem cell cultures in stirred tank bioreactors, presenting data towards scalable mass expansion of hiPSCs . Since then Eppendorf further developed its bioreactor design to suit the special needs of stem cells, for example as part of the EU Horizon 2020 research consortium Technobeat (Tools and TECHNOlogies for Breaktrough in hEArtTherapies).
With hands-on experience in stem cell culture using bioreactors, our lab applications team has authored comprehensive application notes on stem cell bioprocessing, allowing our customers to leverage this expertise through readily accessible, practical guidance. Have a look at some of them here:
With hands-on experience in stem cell culture using bioreactors, our lab applications team has authored comprehensive application notes on stem cell bioprocessing, allowing our customers to leverage this expertise through readily accessible, practical guidance. Have a look at some of them here:
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Application notes on stem cell bioprocessing from the Eppendorf applications labs
PDF 8 MB
Application Note
PDF 1.5 MB
Application Note
PDF 3.3 MB
Application Note
Join the stem cell community!
Organized for the first time in 2017, the Stem Cell Community Day (SCCD) connects researchers from academia and industry across the world, to discuss recent advances and new technologies in the field of stem cell production. With a special focus on the controlled cultivation of stem cells in stirred-tank bioreactors, the SCCD is an optimal place to exchange knowledge and share expertise with scientists around the world.
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