Nichoid: nanoengineered three-dimensional substrate for stem cell expansion
Duration 1/06/2017 – 30/11/2018 – Funded by ERC-PoC-2016 – G.A. nr 754467
NEW Project results available at the CORDIS website
NEW Video with project results (relevant publications are linked at the bottom of this page)
Mesenchymal stem cells (MSCs) raise a great interest for regenerative medicine for many clinical applications such as orthopaedic, plastic and reconstructive surgery, within autoimmune or degenerative disease treatment and as immune-suppressive agents in organ transplantation. In stem cell therapy, cells are injected in the patient after an extensive in vitro manipulation aimed at obtaining a sufficient cell number able to guarantee the therapeutic effect. Currently, stem cell “manufacturing” implies the use of “feeder” cells and additives from animal sources, hampering the clinical use mainly for safety reasons.
In the context of an ERC Consolidator grant (ERC-CoG) that I currently lead, I introduced a novel ground-breaking concept for an easy to use, repeatable, cost-effective, and safe substrate for stem cell expansion, called the “nichoid” substrate, capable of avoiding feeder cells and dangerous additives. The substrate is polymerized with a laser in a biocompatible resin using a frontier nano-fabrication technology called “two-photon laser polymerization” (2PP).
To explore the possibility of an economic exploitation of this invention covered by an Italian Patent submitted in September 2015 and already extended as PCT, the goal of this PoC is to perform a technical and commercial feasibility to move the method developed in the PI’s laboratory during the ERC grant to the market. In particular, I plan to speed up the maturity level of the technology further developing the production process of individual nichoids (fabrication up-scaling by at least a factor of 10, allowing to cover a culture surface of 5 squared cm in five hours), setting of an actionable IPR strategy (including a market assessment), identification of the suitable exploitation strategy for valorising the patent/know how (licensing). The nichoid could drastically reduce down to few years the time to market of stem cell products that is currently 20 years.
Musi CA, Colnaghi L, Giani A, Priori EC, Marchini G, Tironi M, Conci C, Cerullo G, Osellame R, Raimondi MT, Remuzzi A, Borsello T. Effect of 3D Synthetic Microscaffold Nichoid on the Morphology of Cultured Hippocampal Neurons and Astrocytes. Cells. 2022 Jun 23;11(13):2008. doi: 10.3390/cells11132008
Carelli S, Giallongo T, Rey F, Barzaghini B, Zandrini T, Pulcinelli A, Nardomarino R, Cerullo G, Osellame R, Cereda C, Zuccotti GV, Raimondi MT. Neural precursors cells expanded in a 3D micro-engineered niche present enhanced therapeutic efficacy in vivo. Nanotheranostics 2021; 5(1):8-26. doi:10.7150/ntno.50633
Raimondi MT, Barzaghini B, Bocconi A, Conci C, Martinelli C, Nardini A, Testa C, Carelli S, Cerullo G, Chirico G, Gottardi R, Osellame R, Remuzzi A, Laganà M, Jacchetti E, Micro structured tools for cell modeling in the fourth dimension, Proc. SPIE 11786, Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V, 117861T (20 June 2021); doi: 10.1117/12.259332
Steimberg, N., Bertero, A., Chiono, V., Dell’Era, P., Di Angelantonio, S., Hartung, T., Perego, S., Raimondi, M.T., Xinaris, C., Caloni, F., De Angelis, I., Alloisio, S. and Baderna, D. (2020) “iPS, organoids and 3D models as advanced tools for in vitro toxicology”, ALTEX – Alternatives to animal experimentation, 37(1), pp. 136-140. DOI https://doi.org/10.14573/altex.1911071
Raimondi MT, Donnaloja F, Barzaghini B, Bocconi A, Conci C, Parodi V, Jacchetti E, Carelli S. Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19. Theranostics 2020; 10(16):7034-7052. doi:10.7150/thno.47406. Available from: doi:10.7150/thno.47406
Rey F, Barzaghini B, Nardini A, Bordoni M, Zuccotti GV, Cereda C, Raimondi MT, Carelli S. Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases. Cells. 2020 Jul 7;9(7):E1636. doi: 10.3390/cells9071636.
Rey F, Pandini C, Barzaghini B, Messa L, Giallongo T, Pansarasa O, Gagliardi S, Brilli M, Zuccotti GV, Cereda C, Raimondi MT, Carelli S. Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction. Int J Mol Sci. 2020 Sep 15;21(18):E6775. doi: 10.3390/ijms21186775
Parodi V, Jacchetti E, Osellame R, Cerullo G, Polli D and Raimondi MT. (2020) Nonlinear Optical Microscopy: From Fundamentals to Applications in Live Bioimaging. Front. Bioeng. Biotechnol. 8:585363. doi: 10.3389/fbioe.2020.585363odi
Perottoni S, Neto NGB, Di Nitto C, Dmitriev RI, Raimondi MT, Monaghan MG. Intracellular label-free detection of mesenchymal stem cell metabolism within a perivascular niche-on-a-chip. Lab on a Chip. Feb 2020. doi:10.1039/d0lc01034k
Zandrini T, Shan O, Parodi V, Cerullo G, Raimondi MT, Osellame R. Multi-foci laser microfabrication of 3D polymeric scaffolds for stem cell expansion in regenerative medicine. Scientific Reports (2019) 9:11761 https://doi.org/10.1038/s41598-019-48080-w