Transplantation of insulin-secreting multicellular spheroids for the treatment of type 1 diabetes in mice.

Abstract

The efficacy of cell-based therapy depends on the function and survival of transplanted cells, which have been suggested to be enhanced by spheroid formation. However, few attempts at spheroid generation from insulin-secreting cells, which may be used to treat type 1 diabetes, have been reported. We therefore developed spheroids from the mouse insulinoma cell line NIT-1 by using polydimethylsiloxane (PDMS)-based microwells with a coating of poly(N-isopropylacrylamide) (PNIPAAm). The prepared NIT-1 spheroids or dissociated NIT-1 cells were transplanted into the subrenal capsule in streptozotocin-induced diabetic mice. NIT-1 spheroids prepared using the PNIPAAm-coated PDMS-based microwells had a uniformly sized spherical structure with a diameter of 200-300μm. The PNIPAAm coating increased cell survival in the spheroids and the recovery of the spheroids from the microwells. In diabetic mice, the transplanted NIT-1 spheroids reduced blood glucose levels to normal values faster than dissociated NIT-1 cells did. Additionally, survival was higher among NIT-1 cells in spheroids than among dissociated NIT-1 cells 24h after transplantation. These results indicate that insulin-secreting NIT-1 spheroids prepared using PNIPAAm-coated PDMS-based microwells are more effective for the treatment of type 1 diabetes than dissociated cells in suspension.

DOI: 10.1016/j.jconrel.2013.10.024

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@article{Kusamori2014TransplantationOI, title={Transplantation of insulin-secreting multicellular spheroids for the treatment of type 1 diabetes in mice.}, author={Kosuke Kusamori and Makiya Nishikawa and Narumi Mizuno and Tomoko Nishikawa and Akira Masuzawa and Kazunori Shimizu and Satoshi Konishi and Yuki Takahashi and Yoshinobu Takakura}, journal={Journal of controlled release : official journal of the Controlled Release Society}, year={2014}, volume={173}, pages={119-24} }