Project: Large scale expansion technology for hematopoietic stem cells - combining engineering with biology.

BACKGROUND_x000D_Transplantation of hematopoietic stem cells is used for cure or ameliorate a large number of different hematologic and genetic disorders. Hematopoietic stem cells (HSCs) are self-renewing multipotent cells able to produce all blood cell lineages and can be obtained from bone marrow (BM), umbilical cord blood (UCB), and mobilized peripheral blood (PB). Among these sources, UCB has recently been the focus of clinical applications due to its relative accessibility, its high number of primitive progenitor cells and its relatively low frequency of graft-versus-host disease. However, due to the low number of CD34 positive cells in UCB, ex vivo expansion is required for engraftment into adult patients. For optimum engraftment, current transplantation requires at least 2,5 million CD34 positive cells per kg patient body weight._x000D_To improve outcomes and extend applicability of UCB transplantation, one potential solution is ex vivo expansion of UCB. An ex vivo expansion process would also significantly be beneficial for the clinical use of HSCs derived from PB. Investigators have used several methods, including liquid suspension culture with various cytokines and expansion factors, co-culture with stromal elements and continuous perfusion systems; however the optimal expansion conditions are still not known. One of the key elements for developing an efficient HSC expansion process, that can be used for clinical scale up of HSCs, is to activate or promote HSC self-renewal divisions. _x000D_Stimulation with electromagnetic field have previously been used to increase cell proliferation of a variety of cell types including stem cell populations. However the major challenge is to combine this technology with the optimal growth conditions and large scale culture formats (bioreactors), eventually leading to a reproducible cost-effective expansion technology for HSCs. The development of ex vivo culture systems that facilitate the expansion of HSCs is crucial to clinical application of these cells. An ex vivo scale-up technology will bring to the market a commercial attractive platform that; 1) will enable the use of e.g. UCB derived HSCs for clinical treatment of especially adult patients, 2) create the opportunity for an unlimited supply of HSCs for drug screening in the pharmaceutical industry. _x000D__x000D_Consortium Plan_x000D_The STEMXpand Consortium is involving two R&D performing SME's (Vabrema BV, The Netherlands and Stemcare A/S, Denmark) and a technological service P, Bioneer A/S, Denmark, which together have the required complementary competencies that are needed for developing an optimal scale-up process for HSCs. _x000D__x000D_Vabrema BV has a patented technology based on ultrashort high intense electromagnetic fields (ECPR Technology), for changing cellular activities. Vabrema has developed cell expansion devices compatible with standard cell expansion formats, thereby introducing ultrashort high intense electromagnetic fields to cell populations undergoing an expansion process. For several cell types, including mesenchymal stem cells, this technology has demonstrated the capability of significantly increasing cell proliferation._x000D__x000D_Stemcare A/S is a private cord blood bank and co-founder of Cord Blood Europe. The scientific staff at Stemcare has extensive experience in quality control analysis of HSCs _x000D__x000D_Bioneer has expertise in general stem cell cultivation and scale-up processes in software-controlled bioreactor formats. In addition Bioneer has established a range of different stem cell analysis, from gene- and protein evaluations to functional assays. Therefore the consortium will have the capabilities to develop a fully scalable expansion process from the initial start-up cultures exposed to ECPR Technology to large scale bioreactor cultures of HSCs. _x000D__x000D_EXPECTED RESULTS_x000D_The expected results include; _x000D__x000D_1. A validated large scale expansion technology for HSCs, based on development covering; _x000D_ - ECPR Technology optimized for HSCs_x000D_ - Bioreactor technology optimized for large scale expansion_x000D_ - Optimized culture conditions for large scale expansion_x000D_2. Quality control evaluation panel in compliance with regulations covering expansion of cells regulated by The European Medical Agency (EMA) _x000D__x000D_The direct beneficiaries will be the two participating SME's who expect a substantial company growth as a result of this project (Vabrema + 100% in employees), and Bioneer who will enrich their research competencies as well as service offerings in relation to stem cell culture processes. The scale-up technology of HSCs will also have direct beneficial effects on clinical departments using HSCs for clinical treatments, as unlimited supply of HSCs will be an oppurtunity. The indirect beneficiares will be the biotech and pharmaceutical companies who will benefit from the scale-up technology as HSCs will be available for drug testing (e.g. drugs that increase ingraftment of HSCs)._x000D__x000D__x000D__x000D__x000D__x000D_

Acronym	STEMXpand (Reference Number: 6485)
Duration	01/10/2011 - 01/10/2013
Project Topic	Vabrema, Bioneer and Stemcare will develop the first scale-up technology for expanding hematopoietic stem cells (HSCs) for both clinical use and for pharmaceutical testing.
Project Results (after finalisation)	The primary aim of the STEMXpand project was to develop an efficient and reproducible technology for expanding hematopoietic stem cells (HSCs) from humans. These unique stem cell populations are highly efficient for the treatment of several blood cancer forms as well as certain immunological conditions. Both private and public blood banks are highly interested in applying such technologies as expansion of HSCs isolated from either peripheral blood or umbilical cord blood would have a major impact on the ability to treat a wider range of patients. In addition to these clinical areas of use, both biotech and pharma companies as well as the life science research community are interested in using human HSCs for a wide range of exploitative projects and drug development purposes, where HSCs is the central cell type. _x000D__x000D_The STEMXpand project aimed at using medical device technology and/or with biological approaches to develop an efficient HSC expansion technology. _x000D_The consortium Ps succeeded in the development of an HSC expansion platform that has proven to be applicable to both frozen and fresh blood samples (both umbilical cord blood and peripheral blood samples). With the expansion platform it is possible to expand HSCs to a high cell number while retaining their phenotype (based on classical surface marker expression; e.g. CD34, CD133). The approach is primarily based on a combination of biological cues, including vitamins, growth factors and small molecules and specific process paramerters. With the platform it is possible to isolate HSCs from a patient/donor and expand the HSCs in the laboratory. This approach has the potential to benefit a variety of treatments in the future._x000D_The expansion platform has been presented at several scientific conferences and the technology has been described in several biotechnological magazines.
Network	Eurostars
Call	Eurostars Cut-Off 6

Project partner

Number	Name	Role	Country
3	Bioneer A/S	Partner	Denmark
3	Stemcare A/S	Coordinator	Denmark
3	Vabrema BV	Partner	Netherlands