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Pluripotent stem cell resources for mesodermal medicine

Description: Harnessing the capacity of pluripotent stem cells (PSCs) to produce functional cell types with precision and at scale will enable new treatment modalities for degenerative diseases. A major target for such therapies is mesodermal tissue, muscle, bone and cartilage. The goal of PluriMes is to create a bioengineering platform for directing PSCs into specific classes of mesodermal/mesenchymal progenitor. The project pulls together stem cell experts, genetic engineers, developmental biologists, cell therapy pioneers, bioengineers and specialist SMEs in a cross-disciplinary collaborative effort. Close-working between partners will be maximised through specialist workshops, laboratory exchange schemes, regular workpackage meetings, and joint Deliverables. The concept underlying PluriMes is that refined control of early fate decisions to produce correctly specified progenitors will be obtained through confronting developmental principles with engineering logic. We aim to define ground states and resolve issues of hierarchy, heterogeneity and stability in order to provide standardised PSC and mesodermal progenitor cell populations. A toolbox of fluorescent reporters will be developed for live cell tracking. Cutting edge bioengineering approaches will be implemented for dynamic topological administration of morphogens, matrices, small molecule modulators and siRNAs in 2D and 3D contexts. Through SME involvement, culture systems will be optimised for specification and subsequent stable expansion of mesodermal progenitors. The capacity of PSC-derived mesodermal cells for maturation into skeletal muscle, bone and cartilage will be tested in vitro and in vivo using lineage reporters. Potency will then be evaluated in pre-clinical disease models. Scale up protocols will be implemented in partnership with SMEs using the latest bioreactor technologies. Finally, GMP compliance and validated applicability to clinical grade stem cells will underpin future cell therapy propositions.
Amount: €6,000,000
Funding type: research
Funder scheme: FP7 - CP-FP
Start date: 2014-02-01
End date: 2018-01-31
Institution: THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Funded outputs count: 31
Funder award ID: 602423
OpenAlex ID: G3293281035
2021 · Ziad Al Tanoury, John F. Zimmerman, et al. · Proceedings of the National Academy of Sciences · 74
2020 · Xin Cao · Leiden Repository (Leiden University)
2020 · Benjamin T. Dodsworth, Klas Hatje, et al. · Scientific Reports · 16
2019 · Nicholas Bredenkamp, Jian Yang, et al. · Stem Cell Reports · 118
2019 · Elisa Giacomelli · Leiden Repository (Leiden University)
2019 · Nicholas Bredenkamp, Giuliano Giuseppe Stirparo, et al. · Stem Cell Reports · 104
2019 · Maria Rostovskaya, Giuliano G. Stirparo, et al. · Development · 129
2018 · Heather B. Steele-Stallard, Luca Pinton, et al. · Frontiers in Physiology · 67
2018 · The International Stem Cell Initiative, Thomas F. Allison, et al. · Nature Communications · 125
2017 · Juan Antonio Guadix, Valeria V. Orlova, et al. · Stem Cell Reports · 70
2017 · Verena Schwach, Arie O. Verkerk, et al. · Stem Cell Reports · 59
2017 · Jan Barfoot, Kate Doherty, et al. · Seminars in Cell and Developmental Biology · 5
2017 · Ge Guo, Ferdinand von Meyenn, et al. · Development · 318
2017 · Qi-Long Ying, Austin Smith · Stem Cell Reports · 46
2017 · Oliver Baker, Sarah Tsurkan, et al. · Nucleic Acids Research · 45
2016 · Robert Passier, Valeria Orlova, et al. · Cell stem cell · 140
2015 · Valeria V. Orlova, Susana Chuva de Sousa Lopes, et al. · Cytokine & Growth Factor Reviews · 12
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