NANOII

Nanoscopically-guided induction and expansion of regulatory hematopoietic cells to treat autoimmune and inflammatory processes

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 Obiettivo del progetto (Objective)

'We propose a multidisciplinary program, focusing on the development of novel approaches for directing the differentiation, proliferation and tissue-tropism of specific hematopoietic lineages, using micro- and nano-fabricated cell chips. We will use advanced nanofabricated surfaces functionalized with specific biomolecules, and microfluidics cell chips to specify and expend regulatory immune cells for treating diverse inflammatory and autoimmune disorders in an organ- and antigen-specific manner. The proposed cell-chip will create ex-vivo microenvironments mimicking in-vivo cell-cell interactions and molecular signals involved in differentiation and proliferation of hematopoietic cells. Cell chip development and optimization will be supported by high throughput microscopy to select for optimal conditions. “Educated” cells will be employed for in vivo experiments in mice and the methodology will be further adapted for human cell populations, and applied for clinical diagnosis and therapy as well as the developments of clinically-relevant devices. Regulatory T-cells are extremely promising cells for treatment of inflammatory and auto-immune disease, as well as for tolerance induction in organ transplantation. To be effective they must be produced conveniently, at large numbers with an optimally tuned phenotype. The methodology is suggested to overcome current obstacles in obtaining therapeutically significant numbers of T cells. We propose to apply the suggested methodology for treating different inflammatory or autoimmune diseases including type-1 diabetes using targeted immunotherapeutic approaches. Developing new methods for producing large numbers of finely-tuned and tissue-targeted regulatory cells will make this approach clinically viable. This novel methodology can be extended to directing differentiation of other specific T-cell and hematopoietic lineages, with possible applications for targeting other autoimmune diseases and treating tumors or graft rejection.'

Introduzione (Teaser)

European scientists followed a novel approach for obtaining regulatory T cells that could be used for therapy. Using nanotechnology, they formulated chips for growing and differentiating cells which could be scaled up for clinical studies.

Descrizione progetto (Article)

Regulatory immune cells and especially T cells are emerging as a promising approach for treating various autoimmune or inflammatory conditions such as Type-1 diabetes mellitus (T1DM) and inflammatory bowel disease. Optimising the procedures for cell culture of these cells is of utmost importance before proceeding with clinical applications.

Scientists in the EU-funded http://www.mf.mpg.de/NanoII/ (NANOII) project proposed a novel method for differentiating hematopoietic cells down a specific lineage. They developed micro-and nanofabricated surfaces functionalised with specific molecules where cells could bind, differentiate and expand. Gold nanoparticles, initially attached to glass surfaces were subsequently coated with various molecules capable of supporting the growth and differentiation of regulatory T cells or dendritic cells.

The NANOII cell chips were designed to recreate the in vivo microenvironment mimicking cell-cell-interactions and molecular signals. To this end, the microfluidic platforms contained chemical gradients of biologically active compounds in solution. To validate the phenotype and morphology of the generated cells, a high-resolution microscopy was set up alongside multi-parameter algorithms for following cell differentiation. Furthermore, regulatory T cells were screened for their efficacy in preventing inflammatory bowel disease in experimental models.

Finally, the whole process was scaled up to generate high numbers of antigen-specific regulatory T cells under clinical-grade conditions for cellular therapy. Although the deliverables of the project present with high commercial exploitability, further optimisation of the culture conditions to good manufacturing practice (GMP) standards was considered vital for obtaining approval for clinical trials.

Nonetheless, the NANOII approach offered a new perspective for clinical diagnosis and therapy of important diseases. Immediate plans include obtaining a GMP-compatible, cell-based medicinal product for patients with T1DM.