The islets are wrapped with a shell material similar to that of drug capsule preparations to make a "islet capsule".
In this way, the islets in the capsule are protected from the immune system and at the same time well release insulin, which regulates blood sugar in diabetic patients.
——Wang Yi, Researcher, Institute of Organ Transplantation, Affiliated Hospital of University of Electronic Science and Technology of China, Sichuan Provincial People's Hospital
◎Luo Hongyan Chenke
Recently, the team of Professor Leo Biller from the Faculty of Medicine of the University of Fribourg, Switzerland, and the team of Professor Wang Yi from the Institute of Organ Transplantation, Affiliated Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, jointly wrote a report on Type 1 for the official journal of the International Federation of Immunological Societies. A review article on new advances in the treatment of diabetes mellitus (T1DM).
Based on the synthesis of various experimental articles on islet microencapsulation published in recent years, this article looks forward to the future development direction of islet microencapsulation technology.
How is the pancreatic islet microencapsulation technology used in the treatment of diabetes?
What are the advantages of this technology in treating diseases?
What are the future directions for exploration?
Relevant experts have interpreted this.
"Islet Capsule" Provides New Strategy for Diabetes Treatment
Diabetes is no stranger to people. As a disease with no complete cure, it can cause serious chronic damage to the eyes, kidneys, heart, blood vessels, and nerves and the dysfunction caused by them.
Among them, T1DM is an autoimmune disease.
Insulin-secreting beta cells in the pancreas of T1DM patients die due to attack by the autoimmune system, resulting in insufficient insulin secretion and elevated blood sugar.
At present, the medical community mainly adopts islet transplantation to treat T1DM. The donor islets are transplanted into the recipient hepatic portal vein through ultrasound guidance to replace the damaged islet beta cells.
However, although islet transplantation can effectively regulate blood sugar and reduce the occurrence of diabetic complications in a relatively long-term, the immune system still does not spare islet beta cells, which leads to the possibility that the function of transplanted islets may gradually decline over time.
"Using microcapsules to encapsulate islets can effectively isolate immune inflammatory factors, so islet microencapsulation technology has become one of the best strategies for the treatment of T1DM." Wang Yi said.
What is islet microencapsulation technology?
"In layman's terms, islets are wrapped with a shell material similar to drug capsule preparations to make a 'islet capsule'. In this way, the islets in the capsule can not only be protected from the immune system's attack, but also have good health It releases insulin to regulate blood sugar in diabetic patients." Wang Yi said that this technology, also known as islet encapsulation technology, is actually an immune isolation strategy.
Although the islets are "wrapped" with a shell, the islet microencapsulation technology can fully simulate the micro and macro environment of natural islets.
The islet microencapsulation technology uses a microcapsule granulator to wrap biocompatible materials on the outer layer of islets to form small microcapsules with nanometer thickness.
The implanted islets form an immune isolation barrier with the body, allowing the bidirectional diffusion of glucose, oxygen, nutrients, metabolic wastes and signal molecules through the microcapsules, while preventing immune cells and immune active substances from attacking the transplanted islet cells.
Traditional islet transplantation can cause a large reduction in the number of transplanted islets due to inflammatory reactions.
"This technology has many advantages in clinical application. In addition to solving the problem of shortage of donors, it can also avoid the reduction of transplanted islets by reducing or eliminating rejection." Wang Yi said that compared with unencapsulated islets, microsurgery Capsule-encapsulated islets have certain mechanical properties, and are also easy to remove, so as to avoid the loss of functional grafts remaining in the body and causing harm to people.
Combining two hydrogel materials to take advantage of their respective strengths
The development of islet microencapsulation technology has benefited from the continuous improvement of packaging materials.
As a kind of "cell capsule shell", the porosity, properties and composition of the encapsulating material play an important role in the conformal encapsulation of pancreatic islets.
"The pores of the material must be the optimal size to allow nutrient exchange but prevent the occurrence of immune responses." Wang Yi said that the diameter of organic metabolites is 0.05-1 nanometer, while the diameter of globular proteins is 2-10 nanometers, so the package The pore size of the islet microcapsule material should reach 10 nanometers to facilitate the diffusion of small and large molecules, such as oxygen, nutrients and growth factors.
At present, the hydrogel materials for making microcapsules are divided into natural hydrogels and synthetic hydrogels.
Natural hydrogels mainly include polysaccharides (alginate, agarose, chitosan, etc.) and polypeptides (collagen, poly-L-lysine).
Wang Yi said that alginate was the first material used to make microcapsules and is still the most popular microencapsulation material.
However, because it is extracted from marine brown algae, the residual impurity protein, polyphenol, endotoxin, etc. will affect the biocompatibility of the material, which becomes the main factor restricting its clinical application.
"Natural hydrogels have good biocompatibility and low production costs, but under physiological conditions, their stability is weak." Compared with natural hydrogels, synthetic hydrogels (such as polymer Ethylene glycol, polymethyl methacrylate) can control the material properties in terms of pore size, mechanical strength and elasticity, so that it has more suitable pores, higher mechanical resistance and elasticity, but its disadvantage lies in Low biocompatibility and high production cost.
The two materials have their own advantages and disadvantages. Can they take advantage of their own strengths to achieve the effect of one plus one greater than two?
Wang Yi said that scientists are currently trying to improve the deficiencies of natural hydrogels while maintaining their beneficial properties through the combination of natural hydrogels and synthetic hydrogels.
This is also one of the current research directions of islet microencapsulation technology.
She said that existing attempts include: coating the surface of alginate capsules with methoxy polyethylene glycol (mPEG) to reduce immune responses; PEGylation by poly-L-ornithine (PLO) Modified alginate microencapsulated islets can have lower immune response and longer in vivo survival time of islets; adding oligopeptide RGD to polyethylene glycol (PEG) hydrogel can reduce immune rejection; Polylactic-glycolic acid polymer (PLGA) nanofibers combined with FTY720 (a small molecule that promotes blood vessel formation) or vascular endothelial growth factor (VEGF) can also induce the angiogenesis of transplanted islets and improve the hypoxia of transplanted islets state.
New packaging technology may become the direction of future exploration
In 1994, the team of Prof. Xinxiang Huang, who taught at UCLA School of Medicine, reported the world's first microencapsulated human islet transplantation. A diabetic patient received alginate-poly-l after allogeneic kidney transplantation. - Lysine-alginate microencapsulated islets were transplanted intraperitoneally and the encapsulated islets were reinfused 6 months after islet transplantation.
The patient, however, had not been able to achieve insulin independence for nine months post-transplant and still required daily insulin injections.
Since then, many scientific research institutions and companies around the world have carried out research and clinical trials on islet microencapsulation technology. Although diabetic patients recovered normal blood sugar and got rid of the dependence on exogenous insulin in a short period of time, they still returned to the pre-transplantation level. state of need for exogenous insulin supplementation.
"The progress of islet microencapsulation technology is in full swing, but at present there is no international guideline and expert consensus on microencapsulation of islet, and only a few islet microencapsulation technology has entered the clinical trial stage, and large-scale clinical application is not yet available." Wang Yi said , the size of the microcapsules is strictly limited. When the size of the microcapsules is too large, the islets in the microcapsules will be necrotic due to lack of oxygen and nutrients.
In addition, the implanted microcapsule material can cause a foreign body response, leading to the overgrowth of pericapsular fibrosis caused by host recognition, thereby affecting the entry of nutrients and oxygen into the microcapsules, preventing insulin release and waste discharge, which are all part of this technology. limitations and shortcomings.
At present, the microencapsulation of pancreatic islets and other cells such as liver cells to treat diseases has become a research hotspot in the field of tissue and organ transplantation and regeneration.
"Our future research on microencapsulated materials will mainly focus on exploring new encapsulation techniques to improve the biocompatibility, robustness and graft survival rate of hydrogels," said Wang Yi.
In addition, the currently known hepatic portal vein and intraperitoneal cavity are not ideal sites for microencapsulated islet transplantation. Therefore, finding an immune-privileged area as a microencapsulated islet transplantation site can also effectively solve the loss of islet function and fibrosis caused by immune rejection. formation of.
"With the advancement and development of islet microencapsulation technology, the number of clinical trials of microencapsulated islets for the treatment of diabetes is expected to increase. If more suitable capsule materials and packaging technologies can be found, large-scale production and packaging of islets can be carried out. The cost of transplantation will be greatly reduced. This will bring new hope for curing diabetes." Wang Yi said.