干细胞,糖尿病 z-bo 2020-09-30 288

　　Diabetes is gradually becoming one of the biggest health challenges of our time. According to statistics from the World Health Organization (WHO), one in ten people suffers from diabetes. According to the latest public data, the disease caused 1.6 million deaths in 2016. The direct cause. Since then, the World Health Organization has designated diabetes and cancer, respiratory diseases and cardiovascular diseases as the four main non-communicable diseases, and global health authorities will tackle them.

　　The Ministry of Health of Singapore stated that 400,000 Singaporeans have diabetes. This accounts for 10% of the disease burden in the region. At the same time, an independent study by the National University of Singapore predicts that if current trends continue, there will be 1 million diabetic patients in Singapore by 2050. Singapore’s Minister of Health, Gan Kim Young, was vigilant about the potential consequences of uncontrollable chronic diseases and announced a “fight against diabetes” to prevent the outbreak of the disease. We call on the country to work together to better control symptoms.

　　Stop the wave of diabetes (sugar wave)

　　looks like a simple disease, but there are actually many forms of diabetes. Type I diabetes occurs because an autoimmune response destroys insulin-producing cells called pancreatic beta cells. On the other hand, when the cells stop responding to insulin, type 2 diabetes (T2D) occurs. Little is known about monogenic diabetes (single gene diabetes), which is a rare type of diabetes caused by a single gene mutation.

　　Adrian Theo, a senior researcher at the Institute of Molecular and Cell Biology at the Singapore Institute of Science and Technology, said: "But over time, pancreatic β-cell damage and β-cell death are common features of all types of diabetes. Diabetes drugs can help patients control blood sugar. It can control the pancreas. It cannot even cure or even improve the health of beta cells.” He added that obesity is the main cause of diabetes in the West, but it is the main cause of diabetes in Asia. This factor is pancreatic beta cell disease.

　　This is why Theo's research team believes that the power of stem cells can be used to fight diabetes. Unlike most cells in the body, stem cells have the ability to self-renew and can differentiate into many cell types, including pancreatic beta cells. Therefore, in diabetic patients, stem cells can be used to replace the deceased's pancreatic beta cells, thereby restoring insulin production and glucose regulation in these patients. Teo does not obtain stem cells from embryos, but obtains blood cells and fibroblasts (a type of skin cell) from diabetic patients and reprograms them into human induced pluripotent stem cells (hiPSC). I thought. Then, before these hip cells differentiate into pancreatic beta cells and transplant them into the patient, gene editing can be performed to correct diabetes-related or genetic mutations.

　　TeoLab PhD student BlaiseSuJunLow said: "This method may allow an almost unlimited supply of pancreatic beta cells for cell replacement therapy, because it will be transplanted into patients with their own cells. Another discovery

　　In addition to cell replacement therapy, hiPSC also helps to clarify the underlying molecular mechanism of diabetes. For example, Teo's research team used hipsC from patients diagnosed with MODY (a subtype of monogenic diabetes, a mature-onset diabetes in young people) to control the control of specific genetic networks. I know what to do with pancreas and liver development. These two organs are essential for normal glucose metabolism.

　　The approximate experimental setup is as follows. First, the Teo team induced hiPSC (hereinafter referred to as MODYhiPSC) from MODY patients to differentiate them into preendometrial follicles and human pancreatic precursor cells-human embryos eventually reach the pancreas and liver. Some of them produce beta-like cells in the pancreas. They compared the gene expression patterns of MODYhips C-derived preendoderm cells, pancreatic precursor cells, and β-cell-like cells with normal people. Therefore, the Teo team discovered a mutation in a gene called HNF4A that may cause a decrease in the overall expression of genes that recognize the development of the pancreas and liver in MODY1 patients. Importantly, Teo pointed out that unlike in humans, mice with mutant copies of HNF4A do not develop diabetes, so it is impossible to use a mouse model to make this discovery.

　　Teo explained: "Currently, there are more than 14 forms of MODY, each of which is caused by mutations in different genes (HNF4A, HNF1A, PAX4, INS, etc.). Interestingly, many of them are found in the MODY gene. The genetic mutation of the disease. He said it is related to type 2 diabetes (the most common type of diabetes) and affects about 90% of diabetic patients.” Teo said that the findings of MODY patients are related to the pathophysiology of T2D. He added that it might be so. ..

　　In addition, by using hipsC as a platform for genetic screening, scientists may be able to successfully divide patients into different treatment groups. At the same time, it is possible to determine new drug targets based on this screening method. This brings the ideal of diabetes precision medicine closer to reality. The universal solution is not suitable for all patients, and the prescription should be based on the inherent genetic defects of each diabetic patient.

　　Continuous researchMany laboratories around the world are using HiPSC for genetic screening and drug discovery of diabetes. On the other hand, treatments that include the use of hipsC to replace abnormal pancreatic beta cells still have a way to go before they are approved for clinical use. Low recalled that the plan to differentiate hipsC into pancreatic β cells was not 100% effective, and there may still be some residual pluripotent cells hidden in the differentiated pancreatic β cells. .. She said that transplanting pancreatic beta cells into these pluripotent cells can also cause malformations, and this tumor can cause life-threatening complications. Teo further pointed out that the exact function of pancreatic β cells produced by hipsC has not been fully confirmed. "It must function like real human pancreatic islet beta cells or pancreatic islets, otherwise individual glucose levels will not be properly regulated and pose a health risk."

　　1 People are paying attention to gene editing technology. (For example, the popular CRISPR/Cas9 system) is safe when correcting genetic mutations associated with diabetes. Unless Teo can rule out the unexpected or unexpected off-target results of CRISPR-mediated genome editing, the possibility of genetically engineered hipsC for cell replacement therapy is still limited.

　　Despite these challenges, the Teo team is still optimistic and not afraid. He said: “For hiPSC-based cell therapies that have not yet undergone genome editing, multiple clinical trials are currently underway to evaluate the ability of these hiPSCs to produce pancreatic beta cells and regulate blood sugar levels. Optimize your laboratory and many others around the world The laboratory aims to eliminate residual hiPSC and improve the function of pancreatic β cells produced by hipsC. Their behavior is the actual insulin of the pancreatic islets. They strive to be similar to secretory cells."

　　In the fight against diabetes, Theo emphasized the importance of close cooperation between the laboratory and the clinic. He said: "We believe that working with clinicians and pancreatic transplant surgeons is a mutually beneficial model that will ultimately help transform scientific efforts into therapeutic values for patients and society."