Project

MICRONICHE

Goal: There is a growing interest in adult stem cells, especially from bone marrow, for regenerative medicine. Hematopoietic stem cells, a type of bone marrow 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 until prompted to differentiate. The stem cell niche provides structural and trophic support and the appropriate homeostasis to regulate stem cell function. 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. In order to expedite for basic studies of bone marrow stem cells, and further translational implementation, any realistic approach to the native stem cell niche requires: to engineer a biomimetic 3D-microenvironment, and then to develop artificial microniches with the key functional features reconstructed. High-throughput microfluidic technology offers high promise, however, adaptation to accommodate adult stem cells in artificially fabricated niches remains still a challenge. Microfluidic-assisted culture systems should not only allow maintaining cell homeostasis through biochemical and mechanical stimulation, but also modulating adult stem cell renewal and differentiation through microscale patterning of cells and extracellular materials in biomimetic microniches. This project aims at the microfluidic reconstruction of an artificial stem cell niches. In this proof-of-concept, a bone marrow stem cell microniche with tunable size, material and topography will be developed by integrating novel fabrication microfluidics with material engineering

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 705163).

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Cryopreservation of Natural Killer cells in droplets
Conference Paper
  • Jul 2022
Current Natural Killer (NK) cryopreservation protocols lead to loss of NK cell viability and functionality (1,2), highlighting the need for more efficient protocols. 3D cryopreservation enhances the post-thaw viability and functionality as compared with cell suspension and monolayer culture methods (2). To our knowledge, there is no attempt to preserve NK cells using droplet-based microfluidics. We have applied our Microniche platform (3) to generate 3D NK cell laden alginate droplets with improved cell protection. Our preliminary data reveals high viability of cryopreserved NK cells in single-layer beads using DMSO in FBS, opening new possibilities towards NK cell cryopreservation with minimum cell loss and damage during freeze-thaw process.
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Microfluidic assisted engineering of multilayered microcapsules for 3D stem cell culture
Conference Paper
  • Jan 2020
Regenerative medicine has increasingly made use of adult stem cells in the last years (1, 2). Micro-engineering a biomimetic three dimensional structure provides a realistic approach for stem cell niche studies, and further translational applications. A promising approach for engineering artificial stem cell niches is provided by high-throughput microfluidic technologies. In this work, a droplet-based microfluidic-assisted encapsulation device for the generation of multi-layered cellular structures on demand using alginate and Puramatrix is presented. This novel technology is based on gravity-driven flows, passive mixing principle and a gelation system where the use of a double laminar oil flow where only one contains the cross-linking agent allows both the uniform gelation of the inner core and the continuous generation of a stream of cross-linked hydrogel beads. The soft consecutive coating of the inner core with a second and a third layer without exposing the encapsulated cells to external forces that might reduce their viability represents a promising technology towards 3D stem cell encapsulation. Furthermore, we demonstrate the suitability of the presented technology for encapsulation of stem cells by using human Mesenchymal Stem cells (hMScs) and human Hematopoietic stem cells (hHScs). Preliminary results demonstrate a niche model capable of mid-term culture of primitive hHScs in a microfluidic environment. Therefore, the presented method could apply for the artificial reconstruction of the stem cell niche components as an efficient approach to study stem cell behaviour in vitro under controlled conditions, opening a wide field of potential applications within uTAS for 3D cell culture and tissue engineering applications.
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A Multifunctional Microfluidic Platform for Generation, Trapping and Release of Droplets in a Double Laminar Flow
Article
  • Apr 2017
Droplet microfluidics, involving micrometer-sized emulsion of droplets is a growing subfield of microfluidics which attracts broad interest due to its application on biological assays. Droplet-based systems have been used as microreactors as well as to encapsulate many biological entities for biomedical and biotechnological applications. Here, a novel microfluidic device is presented for the generation, trapping and release of aqueous including hydrogel droplets in a double laminar oil flow. This platform enables the storage and release of picoliter-sized droplets in two different carrier oils by using hydrodynamic forces without the need of electrical forces or optical actuators. Furthermore, this design allows droplets to be selectively and simultaneously exposed to two different conditions and collected on demand. Successful encapsulation of hepatoma H35 cells was performed on-chip. Viability of cell-laden droplets was performed off-chip to assess the potential applications in 3D encapsulation cell culture and drug discovery assays.
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There is a growing interest in adult stem cells, especially from bone marrow, for regenerative medicine. Hematopoietic stem cells, a type of bone marrow 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 until prompted to differentiate. The stem cell niche provides structural and trophic support and the appropriate homeostasis to regulate stem cell function. 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. In order to expedite for basic studies of bone marrow stem cells, and further translational implementation, any realistic approach to the native stem cell niche requires: to engineer a biomimetic 3D-microenvironment, and then to develop artificial microniches with the key functional features reconstructed. High-throughput microfluidic technology offers high promise, however, adaptation to accommodate adult stem cells in artificially fabricated niches remains still a challenge. Microfluidic-assisted culture systems should not only allow maintaining cell homeostasis through biochemical and mechanical stimulation, but also modulating adult stem cell renewal and differentiation through microscale patterning of cells and extracellular materials in biomimetic microniches. This project aims at the microfluidic reconstruction of an artificial stem cell niches. In this proof-of-concept, a bone marrow stem cell microniche with tunable size, material and topography will be developed by integrating novel fabrication microfluidics with material engineering
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 705163).
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