Editors' ChoiceTissue Engineering

Transforming lung to treat type 1 diabetes

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Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaaw5324
DOI: 10.1126/scitranslmed.aaw5324


A tissue engineering strategy repurposes lung tissue for islet transplantation.

Patients with type 1 diabetes (T1D) suffer from a loss of their insulin-producing cells. An ideal solution would be to transplant insulin-producing islets to supply insulin on demand, instead of taking shots for life. However, the efficiency and longevity of this procedure is still limited because the transplanted islets do not receive sufficient blood supply and often fail to engraft. Here, Citro et al. engineered a vascularized islet organ using repurposed lung tissue to provide superior performance for islet transplantation.

The authors first identified a striking similarity in the vascular framework between lung and pancreas. The molecular compositions of the two tissue scaffolds resembled each other, with lung possessing several essential proteins that can support islet survival and function. The authors removed all the cells from the lung and used the remaining scaffold to form blood vessels. The alveoli were then filled with islets through the airways without disrupting the structure. They optimized a medium to support islet survival, blood vessel integrity, and optimal insulin production after prolonged culture. With long-term culture, a continuous vascular network was formed between the lung framework and the islets.

The researchers showed that the artificial organ responded to high - but still healthy - glucose concentrations with a normal insulin release profile in vitro. The mature artificial organs produced more total insulin than both the immature ones and cultured islets. The artificial islet organ also dealt with two glucose hikes in a day without any decay in performance. The authors then transplanted the organ into diabetic rats. Compared with standard islets, the transplanted vascularized islet organ demonstrated higher insulin release and more rapidly reduced blood glucose. The artificial organ’s structure and vascular network also remained intact after being directly exposed to arterial blood pressure for one hour. To demonstrate long-term functionality, the researchers transplanted the islet organ under the skin of diabetic mice. The vascularized islet organ still outperformed standard and improved transplantation procedures, requiring no insulin supplements upon transplantation and reversing diabetes in 92% of recipients as compared with 0% and 40% in the other groups. After a month, the blood supply in this organ was still better than in the other implants.

Although more studies are required to evaluate longer term functionality and immunogenicity under realistic clinical settings, overall, Citro et al. showed a promising tissue engineering design and a new strategy for islet transplantation that could bring new hope to the patients with T1D.

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