Micro engineering the hematopoietic stem cell niche for regenerative medicine

Hematopoietic stem cell (HSC) transplant is a well-known therapy for the treatment of some haematological diseases. However, this treatment is often compromised by the limitations on achieving a suitable supply of HSC from some donor tissues. Therefore, many efforts have been developed towards ex vivo expansion of the HSC population in order to overcome this limitation. Hematopoietic stem cells alone cannot be expanded in vitro; in vivo, they reside in a microenvironment known as a niche that maintains them in a quiescent state. Additionally to regulatory factors in these stem cell niches, a number of environmental and mechanical signals arising from the extracellular matrix are crucial regulators of stem cell fate.The presented device constitutes a reliable and robust tool to generate double hydrogel concentric structures on demand. The generation technique uses only passive forces making the procedure specially suitable for the generation of cell constructs. The chip geometry can be modified to suit other range of bead sizes or layer number in a suitable manner. The ability to generate controlled size cell laden structures whilst retaining formation and extraction capacity opens a wide field of potential applications within uTAS for tissue engineering applications. Furthermore, this droplet-based niche mimicry strategy reveals optimal requirements for stem cell maintenance ex vivo and further expansion for clinical applications.