RESUMEN
Human pluripotent stem cells (hPSCs) represent an excellent cell source for regenerative medicine and tissue engineering applications. However, there remains a need for robust and scalable differentiation of stem cells into functional adult tissues. In this paper, we sought to address this challenge by developing magnetic microcapsules carrying hPSC spheroids. A co-axial flow-focusing microfluidic device was employed to encapsulate stem cells in core-shell microcapsules that also contained iron oxide magnetic nanoparticles (MNPs). These microcapsules exhibited excellent response to an external magnetic field and could be held at a specific location. As a demonstration of utility, magnetic microcapsules were used for differentiating hPSC spheroids as suspension cultures in a stirred bioreactor. Compared to standard suspension cultures, magnetic microcapsules allowed for more efficient media change and produced improved differentiation outcomes. In the future, magnetic microcapsules may enable better and more scalable differentiation of hPSCs into adult cell types and may offer benefits for cell transplantation.
RESUMEN
The ability to maintain functional hepatocytes has important implications for bioartificial liver development, cell-based therapies, drug screening, and tissue engineering. Several approaches can be used to restore hepatocyte function in vitro, including coating a culture substrate with extracellular matrix (ECM), encapsulating cells within biomimetic gels (Collagen- or Matrigel-based), or co-cultivation with other cells. This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids. These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors. We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes. We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor (HGF) into microcapsules and inhibiting transforming growth factor (TGF)-ß1 signaling. Overall, bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering, regenerative medicine, and drug testing applications.