Protecting Transplanted Islets: Engineering Materials for Islet Tissue Transplantation
By: Tiffany Richardson and Rachel Gurlin
To mitigate the biological and lifestyle impacts of constant insulin treatment, scientists, physicians and bioengineers have worked together to develop islet transplantation to reintroduce insulin-making beta cells in T1D patients. The general concept of this procedure is the isolation of islets from a healthy organ donor followed by the infusion of the islets into the portal vein. The transplanted islets then engraft after about two weeks and start to release hormones in response to blood glucose changes. A clinical study found that one-year post-transplantation, 90% of islet recipients achieved A1C’s below 7% (a goal for T1D patients) and had few to no severe hypoglycemic events (SHEs). As time passed, though, 60% of recipients needed some level of insulin therapy again. So why do 60% of these patients need to go back on insulin therapy?
Islet transplantation comes with its disadvantages as well, including the need for recipients to take immunosuppressants for their entire life to prevent the body’s rejection of the transplanted islet tissue. These immunosuppressants have negative side effects such as increased cancer risk, kidney damage and others. To avoid the need for immunosuppressant regimens, islet encapsulation is being developed. which gives cells a safe and, in some cases, nutritive environment to hide from the immune system and deliver therapeutic agents. Research has led to the development of methods that combine nutrients and biomimetic materials to improve outcomes of tissue transplantation.
Biomimetic Material Development: Umbilical Cord Scaffolds & Placental Co-Culture
Replacement of diseased and/or damaged tissues is the main goal of tissue engineering. Kumaresan and colleagues recently detailed their efforts to generate a scaffold made from decellularized human umbilical cords. Decellularization methods separate cells from the surrounding extracellular matrix (ECM) to harness the existing growth factors, structural tissue support and other nutrients. This isolated ECM has all the characteristics needed for tissue scaffolds: biocompatibility, biodegradability, cell adhesion and proliferation, high porosity and tissue regeneration promotion. The report details the adaptation of previous decellularization protocols for its application in generating bioactive scaffolds from the human umbilical cord.
Additionally, Kreuder and colleagues described a method to create an in vitro barrier membrane from a well-known barrier organ – the human placenta, and utilized a co-culture of cells from : the trophoblast-derived cell line, primary placental fibroblasts and primary human placental endothelial cells. The various cell types maintained their specific markers throughout the co-culture experiments. This complex cellular environment would potentially supply protection, support for cellular function and a novel ex vivo platform to grow cells. Additionally, the human placenta is typically discarded tissue, making it advantageous over other decellularized scaffolds like lung or pancreas, in which donors are scarce. Repurposing the placenta could provide the optimal environment islets need without taking vital tissue that may be needed elsewhere.
Overall, these studies resulted in the generation of: 1) Successful cellular films on umbilical cord ECM scaffolds, and 2) Barrier tissue from placenta cell co-culture that can be employed to not just protect transplanted tissue, but also sustain and improve tissue function. The biological environment and cellular processes of other tissues such as the placenta and corresponding ECM could help to improve islet function and survival after transplantation in T1D patients.
- National Institute of Diabetes and Digestive and Kidney Diseases. (2016). Islet transplantation restores blood sugar awareness and control in type 1 diabetes. https://www.niddk.nih.gov/health-information/diabetes/overview/insulin-medicines-treatments/pancreatic-islet-transplantation.
- Kumaresan, S., Chokalingam, K., Narasimhachar Sridhar, K., and Veerichetty, V. (2020). Cell microencapsulation technologies for sustained drug delivery: Clinical trials and companies. AIP Conference Proceedings, 2270. https://doi.org/10.1016/j.drudis.2020.11.019.
- Kreuder, AE., Bolaños-Rosales, A., Palmer, C. et al. (2020). Inspired by the human placenta: a novel 3D bioprinted membrane system to create barrier models. Sci Rep 10. https://doi.org/10.1038/s41598-020-72559-6.