MicroNICHE · Microfluidic-assisted fabrication of artifical microniches for bone marrow stem cells

Microfluidic-assisted fabrication of artifical microniches for bone marrow stem cells

This project aims at the generation of an artificial 3D cell structure towards the recapitulation of the hematopoietic stem cell niche (SCN). Hematopoietic stem cells (HSC), a type of bone marrow stem cells (BMSCs), alone cannot be expanded in vitro. The microenvironment in which these cells reside is known as stem cell niche and its this environment which maintains them in a quiescent state . A realistic approach of the stem cell niche would require to engineer a biomimetic 3D-microenvironment, and then to develop artificial microniches with the key functional features reconstructed. High-throughput microfluidic technology offers a suitable technology however adaptation to accommodate adult stem cells (ASCs) in artificially fabricated niches remains still a challenge. Our route to micro engineer these cell constructs by droplet microfluidics offers the possibility of using various biomaterials and the maintenance of the encapsulated cells through the use of passive forces as technology for generating multi-layered hydrogel cell constructs. The main objective of the project is the microfluidic reconstruction of an artificial SCN. For this approach, a droplet-based microfluidic technique is proposed in which a bone marrow stem cell (BMSC) microniche with tunable size, material and topography will be developed. Two physical requisites would be necessary to reconstruct normal HSC function in a artificial stem cell niche, the control of the niche geometry, and the functional reconstruction of the artificial SCN in a mechanically adapted support. These requisites are considered in both presented models comprising various layers of biocompatible hydrogels containing MSCs and HSCs. This approach for the artificial reconstruction of these niche components represents an efficient method to simulate the in vivo situation of HSCs with the goal to study stem cell behavior in vitro under controlled conditions. This tailored coating of an inner hydrogel core extendable to a third coating layer represents a promising technology to reconstruct more complex cell arrangements and mimic better the complexity of the stem cell niche.Therefore, the presented device is a valuable and unique tool towards gaining insights in understanding the regulation factors influencing the stemness maintenance of HScs and more generally, in understanding stem cell behavior in 3-dimensional environments.

Data: CORDIS, © European Union