A 3D-printed microdevice encapsulates vascularized islets composed of iPSC-derived β-like cells and microvascular fragments for type 1 diabetes treatment

Transplantation of insulin-secreting cells provides a promising method for re-establishing the autonomous blood glucose control ability of type 1 diabetes (T1D) patients, but the low survival of the transplanted cells hinder the therapeutic efficacy. In this study, we 3D-printed an encapsulation system containing β-like cells and microvascular fragments (MVF), to create a retrivable microdevice with vascularized islets in vivo for T1D therapy. The functional β-like cells were differentiated from the urine epithelial cell-derived induced pluripotent stem cells (UiPSCs). Single-cell RNA sequencing provided an integrative study and macroscopic developmental analyses of the entire process of differentiation, which revealed the developmental trajectory of differentiation in vitro follows the developmental pattern of embryonic pancreas in vivo. The MVF were isolated from the epididymal fat pad. The microdevice with a groove structure were rapidly fabricated by the digital light processing (DLP)-3D printing technology. The β-like cells and MVF were uniformly distributed in the device. After subcutaneous transplantation into C57BL/6 mice, the microdevice have less collagen accumulation and low immune cell infiltration. Moreover, the microdevice encapsulated vascularized islets reduced hyperglycemia in 33 % of the treated mice for up to 100 days without immunosuppressants, and the humanized C-peptide was also detected in the serum of the mice. In summary, we described the microdevice-protected vascularized islets for long-term treatment of T1D, with high safety and potential clinical transformative value, and may therefore provide a translatable solution to advance the research progress of β cell replacement therapy for T1D.