Transplanting insulin-producing cells along with engineered blood-vessel-forming cells has successfully reversed type 1 diabetes, according to a new preclinical study. With further testing, the novel approach could one day cure the as-yet incurable condition.
The pancreatic islet is the only human tissue that produces insulin in response to rising blood glucose levels. In type 1 diabetes, the immune system attacks and slowly destroys these islets, leading to insulin deficiency. Remarkable progress has been made regarding the transplantation of islets, which remains a promising means of restoring insulin production.
However, a major challenge has been replicating the blood-vessel-rich environment that native islets rely on for survival. Now, researchers from Weill Cornell Medicine (WCM) have led a study where they transplanted islets along with engineered blood-vessel-forming cells – successfully reversing diabetes in mice.
“This work lays the foundation for subcutaneous [under the skin] islet transplants as a relatively safe and durable treatment option for type 1 diabetes,” said the study’s lead author, Ge Li, PhD, a research associate at WCM’s Department of Medicine.
Currently, the common approach to islet transplantation involves injecting islets extracted from a donor pancreas into the hepatic portal vein, typically via a thin needle inserted into the liver through the skin. Once in the liver, the islets lodge in the small blood vessels called sinusoids, where they take up oxygen and nutrients from the surrounding tissue while new blood vessels form over the course of weeks. Many islets can be lost to inflammation, lack of oxygen, and immune attack during this time. To prevent islet rejection, immune-suppressing drugs are given over the long term.
The researchers wanted to develop a less invasive technique that allowed donor islets to be implanted in a site that was more accessible, such as under the skin, and that enabled the islets’ indefinite survival. So, they engineered generic human endothelial cells (ECs), the cells that line the inside of blood vessels, to form reprogrammed vascular ECs, R-VECs. They first tested the R-VECs in a microfluidic device – a tiny ‘lab-on-a-chip’ – and observed that the R-VECs assembled themselves into a network of vessels capable of carrying human blood. When human islets were commingled with human R-VECs, all of the islets embedded themselves in the newly formed vascular network, and the R-VECs formed tiny vessels that surrounded and penetrated the islets. The blood-vessel-fed islets were functional, too, producing insulin in response to the introduction of glucose.
Li et al. 2025
Next, the researchers co-transplanted human islets and R-VECs under the skin of diabetic mice. As they had in the lab, the transplanted pair formed a vascularized islets network. The mice produced human insulin that normalized blood glucose for over 20 weeks. That the effect lasted that long in the mice effectively suggested to the researchers that the islet/R-VEC graft was permanent. Mice that received islets only, without R-VECs, showed significantly lower insulin production levels and insulin secretion was not responsive to administered glucose.
“Remarkably, we found that R-VECs did adapt when co-transplanted with islets, supporting the islets with a rich mesh of new vessels and even taking on the gene activity ‘signature’ of natural islet endothelial cells,” said co-author David Redmond, assistant professor of computational biology research in medicine at WCM.
The next steps are to continue with preclinical trials to ensure the implant is safe and effective.
“Ultimately, the potential of surgical implantation of these vascularized islets needs to be examined for their safety and efficacy in additional preclinical models,” said co-author Dr Rebecca Craig-Schapiro, associate professor of surgery at Weill Cornell.
The researchers hope the novel transplantation approach will be available to people with type 1 diabetes in the next few years.
“[T]ranslation of this technology to treat patients with type 1 diabetes will require circumventing numerous hurdles, including scaling up sufficient numbers of vascularized islets, and devising approaches to avoid immunosuppression,” said Li.
The study was published in the journal Science Advances.
Source: Weill Cornell Medicine
