Islet Transplantation and the Evolving Landscape of Type 1 Diabetes

Millions of people visit Yellowstone National Park each year to experience the great outdoors. The hot springs, canyons, waterfalls, and geysers are home to a diverse ecosystem of flora and fauna. But for 66 years, something was missing from this picture: wolves. Their absence was a direct result of large-scale predator hunting that began in the late 1800s; by 1926, the last wolf pack in Yellowstone had been killed.^[1]  Similar to this historical eradication, the human immune system can attack and destroy insulin-producing β-cells (beta cells) in the pancreas, resulting in an absence of insulin production known as type 1 diabetes.^[2]

The pancreas is an organ along the digestive tract that acts as a gland, secreting important substances. Insulin is a key hormone released by the pancreas, which regulates blood sugar levels. Blood sugar, also called blood glucose, is like the deer and elk in Yellowstone: important for the health of the ecosystem but destructive if unmanaged. Without insulin, blood sugar can become dangerously high or low, which can result in long-term organ damage and failure (e.g., eyes, kidneys, nerves, blood vessels, and heart) or death.^[3,4] Around 2% of the pancreas is made of cell clusters called islets of Langerhans, which contain β-cells and are responsible for maintaining stable blood sugar levels.^[2,5]  The islets are like wolf packs, containing a large number of insulin-releasing β-cells (individual wolves).^[2] In the estimated 2.1 million Americans diagnosed with type 1 diabetes, the immune system mistakenly attacks and destroys the β-cells in the islets, much like humans once hunted wolves, eliminating entire packs they perceived as dangerous.^[2,6] Without functioning islets, the pancreas is unable to produce the required amount of insulin, leading to elevated blood sugar levels that can harm the body over time. This is similar to how the eradication of wolves in Yellowstone led to overpopulation of deer and changed Yellowstone’s ecosystem.

Researchers don’t fully understand how type 1 diabetes develops, but it is widely believed to be influenced by environmental factors that trigger genetic risks in susceptible individuals.^[3]  There is currently no cure for type 1 diabetes. Most patients rely on daily insulin injections for the rest of their lives. Whole pancreas transplants can restore normal blood sugar levels by replacing destroyed islets, but they are a risky and an uncommon treatment option.^[2] As a result, clinical researchers are looking into a third option that avoids daily injection complications and surgical risks: allogeneic islet transplantation.^[2,7]Allogeneic refers to cells, tissues, or organs that are from another individual of the same species. 

The mechanics of allogeneic islet transplantation are similar to the reintroduction of wolves to Yellowstone; in both cases, the effort is to restore the population and environment. Islets with healthy β-cells are taken from a deceased organ donor and injected into the recipient without surgery. Blood transports the islets to the liver, where they make and release insulin into the body. This reintroduction of islets with functioning β-cells restores the body’s ability to produce insulin and manage blood sugar levels.^[8]

It can take months to years for the islets to fully integrate into the body.^[8] During this time, islets can be attacked by the immune system.^[8] Immunosuppressants are typically used to prevent islet rejection, and researchers are advancing the ways in which transplanted islets can be protected,  including by a process called immunoisolation.^[8] One immunoisolation product currently being investigated is Tegoprubart, a monoclonal antibody designed to protect insulin-producing islet cells by calming down or controlling how the immune system reacts to organ or cell transplants.^[9]

Access to allogeneic islet transplantation is severely limited in the United States. This is in part due to a regulatory distinction: under the current Public Health Service Act, allogeneic islets (those from a donor) are considered “biological drugs” and “human cell and tissue products.”^[10,11] This means that therapy providers must submit a Biologics License Application (BLA) to the FDA, which can be a lengthy process full of financial, legal, and logistical barriers.^[10,12]  In November 2025, the ISLET Act was reintroduced in the Senate to redefine “human cadaveric islets” (allogeneic islets) as “organs,” which supporters believe will increase accessibility.^[11] In other countries, human islets are defined as “tissue for transplantation,” and allogeneic islet transplantation has become a standard-of-care option.^[10] In the United States, on the other hand, the small number of allogeneic islet transplants were entirely conducted during clinical trials.^[10] Clinical trials continue to show promise for allogeneic islet transplantation, including new trials studying investigational immunoisolation medications. If the ISLET Act and clinical trials both prove successful, we may have a new way to take a bite out of type 1 diabetes.

Socia Media Strategist, Chase Berger

[1] National Park Service. History of wolf management. National Park Service; Accessed 2026, April 30. https://www.nps.gov/yell/learn/historyculture/wolf-management.htm

[2]Espona-Noguera A, Ciriza J, Cañibano-Hernández A, Orive G, Hernández RM, Saenz del Burgo L, Pedraz JL. Review of advanced hydrogel-based cell encapsulation systems for insulin delivery in type 1 diabetes mellitus. Pharmaceutics. 2019 Nov 12;11(11):597. Accessed 2026, April 30. https://pmc.ncbi.nlm.nih.gov/articles/PMC6920807/

[3] Pang H, Xia Y, Luo S, et al. Emerging roles of rare and low-frequency genetic variants in type 1 diabetes mellitus. J Med Genet. 2021;58(5):289-296. Accessed 2026, April 30.  https://jmg.bmj.com/content/58/5/289

[4] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl 1):S62–S67. Accessed 2026, April 30.  

https://pmc.ncbi.nlm.nih.gov/articles/PMC2613584/ 

[5] Hoang DT, Matsunari H, Nagaya M, et al. A conserved rule for pancreatic islet organization. PLoS One. 2014;9(10):e110384. Accessed 2026, April 30.  

https://pmc.ncbi.nlm.nih.gov/articles/PMC4211668/

[6] Centers for Disease Control and Prevention. Diabetes data and research. Atlanta (GA): CDC; 2026 Jan 21. Accessed 2026, April 30.

 https://www.cdc.gov/diabetes/php/data-research/index.html

[7] Shapiro AMJ, Lakey JRT, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230–238. Accessed 2026, April 30.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3138095/

[8] Kabakchieva P, Assyov Y, Gerasoudis S, Vasilev G, Peshevska-Sekulovska M, Sekulovski M, Lazova S, et al. Islet transplantation-immunological challenges and current perspectives. World J Transplant. 2023 Jun 18;13(4):107–121. doi:10.5500/wjt.v13.i4.107. Accessed 2026, April 30.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10303418/#sec2

[9] Eledon Pharmaceuticals, Inc. Eledon announces updated data from investigator-initiated islet transplant trial of tegoprubart in patients with type 1 diabetes at UChicago Medicine. Irvine (CA): Eledon Pharmaceuticals; 2026 Mar 16. Accessed 2026, April 30. https://ir.eledon.com/news-releases/news-release-details/eledon-announces-updated-data-investigator-initiated-islet

[10] Witkowski P, Philipson LH, Kaufman DB, Ratner LE, Abouljoud MS, Bellin MD, et al. The demise of islet allotransplantation in the United States: A call for an urgent regulatory update. Am J Transplant. 2021 Apr;21(4):1365–1375. doi:10.1111/ajt.16397. PMCID: PMC8016716. Accessed 2026, April 30. 

https://pmc.ncbi.nlm.nih.gov/articles/PMC8016716/#S1

[11] United States Congress. S.3105 - ISLET Act (119th Congress): A bill to regulate human cadaveric islets for transplantation as organs. Washington (DC): Library of Congress, Congress.gov; 2025 Nov 5. Accessed 2026, April 30. 

https://www.congress.gov/bill/119th-congress/senate-bill/3105/text

[12] Weir GC, Bonner-Weir S. Why pancreatic islets should be regarded and regulated like organs. CellR4 Repair Replace Regen Reprogram. 2021;9:e3083. doi:10.32113/cellr4_20213_3083. PMCID: PMC8006072. Accessed 2026, April 30. 

https://pmc.ncbi.nlm.nih.gov/articles/PMC8006072/