Community Research and Development Information Service - CORDIS

FP7

REACH Report Summary

Project ID: 601869
Funded under: FP7-HEALTH
Country: Netherlands

Final Report Summary - REACH (bioREACtor for stem cell tHerapy)

Executive Summary:
The REACH project delivered on its main objectives within the timeframe of the project. Significant results have been obtained in process development, hardware and sensor development, qualification of both biological output and bioreactor design, and dissemination of results.
The project consortium has demonstrated the potential of the bioreactor technology by showcasing its ability to culture clinically relevant cell numbers. The process was developed primarily for bone marrow-derived MSCs, but other cell types, such as fat-derived stem cells, were also investigated along with a GMP isolation protocol. Cells cultured using the Scinus bioreactor technology were thoroughly compared to traditional monolayer cultures. This comparison showed that cells cultured in the new bioreactor were safe, and equally important, that they were functionally and phenotypically similar.
Technical innovations were also developed during the project. Sensor technology was improved by miniaturization and sensor improvements. Smaller sensors allowed an even smaller initial culture volume. Sensor improvements resulted in better performance at low cell numbers or improved stability during sterilization. Additionally, the fragile wired data connection (e.g. optic fibres) were replaced with a wireless data transmission solution, eliminating the sensor failure due to mechanical wear. The new sensors were also tested for biocompatibility.
All partners are committed to exploitation of the project results. Working towards the market introduction of the technologies brought forth by this project, consortium members demonstrated these technologies at various international conferences. Various material to support market introduction (e.g. posters, flyers, website) was produced. A detailed business plan is made by all industrial partners for future exploitation of results.
Since clinical trials for cell therapies cover a wide range of diseases, many of which constitute a large social and economic burden, there will be a need for more efficient production solutions for these complex therapeutic products. The Scinus bioreactor can reduce production costs compared to traditional cell culture approaches. As a result, the novel treatment modalities will more readily be available for patients, representing a major benefit to a very wide patient population.

Project Context and Objectives:
Cell-based therapies are therapies in which cells are used to treat a wide range of diseases such as myocardial infarction, Crohn’s disease and Graft-versus-Host disease. Mesenchymal Stromal Cells (MSCs), a specific cell population found in various tissues (e.g. bone marrow, fat tissues, umbilical cord), are potent candidates because they are relatively easy to obtain and exempt from ethical issues associated with embryonic stem cells. However, due to the low amount of MSCs in donor tissue, cell based therapies rely on cell growth (expansion) in laboratories to reach sufficient cell numbers necessary to treat patients.
The production of cell batches for cell therapy is a costly affair, requiring expensive clean room facilities and labour-intensive procedures. With the expected increase in clinical applications of and research into cell therapies, there is a clear need to make the process of cell expansion cheaper, safer and easier. The REACH consortium brings together industry and academia to develop new technology that enables better, cheaper and easier production of cell therapies.
The REACH consortium will
• Develop innovative bioreactor technology for the production of clinical-grade cell therapy products.
• Ensure that the products produced using this technology adhere to the rigorous quality controls for cell therapies.
• Commit to exploitation of the research results to enable wide-spread use of the innovative technologies developed in this project.

Project Results:
The REACH project delivered on its main objectives within the timeframe of the project. Significant results have been obtained in process development, hardware and sensor development, qualification of both biological output and bioreactor design, and dissemination of results.
The Scinus bioreactor technology is being developed for the cell therapy field, which requires that sufficient cells for a therapy are generated in a single bioreactor run. As a major project result, we showed that a single bioreactor run can yield up to 800 million cells (MSCs), where on average 200 million cells are needed for a single cell therapy application. This result demonstrated that the bioreactor technology can have a place in the production strategy for cellular therapies. While these results were obtained using pre-cultured cells, Ideally cells undergo minimal to no pre-processing before being introduced into the bioreactor system for expansion. The ability to seed a bioreactor directly from unmanipulated cells would be a major advantage over current production processes. As a proof-of-concept of the bioreactor’s ability to support growth of minimally manipulated cells, we seeded a red blood cell-depleted bone marrow biopsy in the Scinus and obtained 80 million cells from a 7 mL biopsy.
While bone marrow-derived mesenchymal stem cells are one of the most common adherent cell types used for cell therapy applications, we also investigated the potential to grow other adherent cell types. Especially fat tissue-derived stem cells (ASCs) are an attractive alternative candidate, due to their ease of harvest. ASCs were also successfully grown using bioreactor-compatible protocols, showing that the bioreactor technology can be used for multiple cell types. Additionally, because ASCs are an attractive source for cell therapies, we optimized cell isolation from fat tissue for use in a GMP manufacturing setting.
Supporting the biological process is newly developed sensor technology that is integrated in the pre-market prototype of the Scinus bioreactor. New sensor patches for biomass, pH and DO measurements were designed for optimized performance. Sensor patches were miniaturized, allowing a further reduction in minimum culture volume. Biomass sensing was improved for the new sensor design, which required an electronic redesign due to the size reduction. Also, pH and DO sensors were made more resistant to sterilization through irradiation, eliminating the need for recalibration post sterilization. All sensor materials were tested for biocompatibility, since they are in direct contact with the cell product. No negative effect of the sensor material was found on the growth characteristics of MSCs.
The Scinus bioreactor is a dynamic culture system, keeping cells, attached to microcarriers, in suspension by rocking the culture bag in which the cells are grown. To ensure robust data transmission from the sensor patches to the controller, a wireless solution was developed. The wireless setup replaces the fragile fibre connections that were sensitive to mechanical failure caused by the rocking of the culture bag. The wireless connection eliminates the risk of loss of signal from the sensors due to broken connections, making the process more robust. This wireless solution incorporates all the newly designed sensors as well as allowing for extension with third party sensors such as temperature.
Although sufficient cells need to be obtained for clinical applications, retaining the cell product’s safety and potency is at least equally important. MSCs cultured in the Scinus bioreactor system were tested for safety and potency using various assays. These assays revealed that MSCs cultured in the Scinus bioreactor system are not phenotypically different from those cultured on standard culture flasks. Moreover, they did not display chromosomal aberrations. Equally important was the conclusion that bioreactor-cultured MSCs retained their functional potency. MSCs were cultured on monolayer, spinner flasks and in the Scinus bioreactor system. All cells displayed similar proliferation inhibition and secretion after cytokine stimulation.
Preparing for commercial exploitation of the developed technology, all industrial partners wrote a business plan that detailed the potential markets and the (route towards) market uptake. Crucial to commercialization is the qualification of the technology for manufacturing under GMP. The bioreactor hardware and software are qualified, while qualification of the single-use bioreactor bag is underway. Further supporting market uptake is the development of end-user support procedures that ease the transition from monolayer culture to the bioreactor process. The procedures were put to the test by the consortium’s academic partner. As another step towards market introduction, the Scinus bioreactor system was displayed to an interested audience at various conferences in the field of Cell Therapy (e.g. International Society for Cellular Therapy Annual Meeting, World Stem Cell Conference).

Potential Impact:
Clinical trials for cell therapies cover a wide range of diseases, many of which constitute a large social and economic burden, such as diabetes, cardiovascular disease and various cancers. With the number of clinical trials for cell therapies still increasing (from approximately 400 MSC trials at the start of the project, to over 600 by its end), there will be a need for more efficient production solutions for these complex therapeutic products. More clinical trials are reaching the later stages of investigation and the first products are already approved, signalling a definite transition from research to commercialization. Consequently, the availability of the Scinus bioreactor technology will come at a time of high interest for new production possibilities. The production costs for these novel treatment options need the be kept in check, since health care costs present an ever-increasing burden on national budgets. The Scinus bioreactor can reduce production costs compared to traditional cell culture approaches. As a result, the novel treatment modalities will more readily be available for patients, representing a major benefit to a very wide patient population.
Various major conferences were attended to inform the cell therapy field of the developments and results of the REACH project. Most notably the bioreactor system was presented to experts in the field at the annual meetings of the International Society for Cellular Therapy, the World Stem Cells conference and the annual meeting of the European Haematology Association. Scientific posters, a public website, and promotional material support the dissemination activities.
Exploitation of the projects results are envisioned for all industrial partners. The exploitation potential goes beyond the use of the bioreactor technology in cell therapy production. New sensor technologies and design will find their markets outside the use in the Scinus. All potential markets and applications are detailed in the business plan that these partners have put together. All partners are committed to further exploitation of the project results in accordance with the business plan.

List of Websites:
http://www.projectreach.eu/

Related information

Contact

Brigitte Wieles, (Project manager)
Tel.: +3171 5263413
E-mail

Subjects

Life Sciences
Record Number: 192589 / Last updated on: 2016-12-13
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