Nature sub-issue: Ultra-thin devices have the potential to transform islet cell transplantation

A quarter-sized device invented by Houston Methodist Church could dramatically alter the course of treatment for type 1 diabetes, a chronic disease that affects millions of Americans for which there is currently no cure
.

In a study published Dec.
26 in Nature Communications, a team led by Houston Methodist sent islet cells and immunotherapy directly into a 3D printed device similar to a bioengineered pancreas, called NICHE
。 The treatment restored healthy glucose levels in animal models, eliminated symptoms of type 1 diabetes for more than 150 days, and avoided serious adverse effects
of anti-rejection therapy by administering immunosuppressive drugs only where the transplanted islet cells were located.

Type 1 diabetes is caused by an autoimmune reaction that destroys the insulin-making cells
in the pancreas.
It can also lead to kidney failure
.
Daily insulin injections are the most routine treatment, but tightly controlling blood sugar levels can still be challenging and cumbersome for patients
.
In addition, in more severe cases, patients may need pancreatic and kidney transplants, or they may be eligible for islet cell transplants, which are collected, processed, and transplanted into the liver of a person with type 1 diabetes
.

These transplants can help improve a patient's symptoms; However, as with all organ transplants, one of the biggest challenges is the need to use immunosuppressive drugs for the rest of their lives to avoid transplant rejection
.
Lifelong immunosuppression can predispose patients to infectious diseases and increase the risk of certain types of
cancer.

Created by the Department of Nanomedicine at the Houston Methodist Research Institute, NICHE is a flat device placed under the skin that consists of a bank of cells for islets and a library of surrounding drugs for local immunosuppressive therapy
.
This is the first platform to combine direct vascularization and local immunosuppression into a single implantable device for allogeneic islet transplantation and long-term type 1 diabetes management
.
Direct vascularization is the basis for
the nutrients and oxygen needed to maintain the survival of transplanted islet cells.

Corresponding author Dr.
Alessandro Grattoni, director of the Division of Nanomedicine at the Houston Methodist Institute, said: "A key result of our study is that local immunosuppression is effective
for cell transplantation.
" "This device has the potential to change the way patients are managed and have a huge impact
on treatment outcomes and improving patients' quality of life.
"

Niche includes ports to supplement the required medications
.
The researchers repopulated the drug library every 28 days, which is comparable
to other long-acting drugs used clinically to prevent migraines or treat HIV.

Grattoni's team is working to bring the NICHE technique to clinical use, which may only require drug replenishment
every six months.
The refilling capacity of the NICHE technique allows long-term use
in patients.
In addition, changing the drug formulation or concentration can extend the replenishment interval to once a year, consistent with
regular doctor visits.

Grattoni and his collaborators will expand this research in the coming years, with the ultimate goal of testing the safety
of NICHE in humans in about three years.
Grattoni's nanomedicine lab at Houston Methodist DIST focuses on implantable nanofluidic platforms for controlled and long-term drug delivery and cell transplantation to treat chronic diseases
.

This research was supported by grants from the Juvenile Diabetes Research Foundation (1-no-2018-595-a-n), the Vivian L.
Smith Foundation, the Houston Methodist DIST Institute, the Diabetes Institute, and the National Institutes of Health (NIDDK R01DK132104
).