[Nature Sub-Journal] A new breakthrough in type 1 diabetes: The new method actually makes the differentiation rate of pancreatic islet β cells as high as 80%?

This article is original by Translational Medicine.
Please indicate the source for reprinting.
Author: Catalina Introduction: In the past two decades, great progress has been made in the field of islet β-cell replacement therapy as a treatment for diabetes
.

Now, scientists have discovered that the chemical combination enhances the clusters of 3D pancreatic progenitor cells derived from human pluripotent stem cells into functional β cells, which can make the differentiation rate of β cells up to 80%
.

Type 1 diabetes is caused by insufficient or lack of insulin metabolism in the patient's body.
Under normal circumstances, more than 80% of pancreatic islet β cells in diabetic patients are destroyed.
There is currently no cure, and it is difficult to control for most patients.

.

Recently, researchers from the Salk Institute published a paper titled "Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells" in the top journal Nature Communications
.

They developed a new method for efficiently producing pancreatic β cells: ten chemicals enhance the clustering of 3D pancreatic progenitor cells derived from human pluripotent stem cells into functional β cells, which can make the differentiation rate of β cells up to 80%
.

In addition, when these beta cells were tested in a mouse model of type 1 diabetes, the animals' blood sugar was controlled in about two weeks
.

Stem cells are a group of primitive cells that can be expanded infinitely, replicated and renewed indefinitely.
They exist in various parts of the human body and are being used for the treatment of various diseases due to their excellent regenerative ability.

.

In recent years, extensive research has been conducted on the therapeutic potential of stem cells in the treatment of diabetes and related complications
.

Beta cells are popular metabolic cells in the body's insulin metabolism
.

According to the repair of the islets, stem cells can ① make the pancreatic islets create new pancreatic islet β cells; ② according to the immediate repair of the pancreatic β cells, make it have the function of metabolizing insulin; ③ according to the factors caused by the stem cells, stimulate the regeneration of pancreatic β cells
.

In addition, the transplantation of stem cells can increase the sensitivity of intracellular glycoproteins, promote the fusion of islet protein kinase and insulin, and reduce the resistance of insulin, thereby achieving the goal of eradicating diabetes
.

In the past two decades, great progress has been made in the field of islet β-cell replacement therapy as a treatment for diabetes
.

In this study, the researchers aggregated pancreatic progenitor cells derived from human pluripotent stem cells (hPSCs) into a 3D structure
.

They also used various growth factors and chemicals to simulate the development of the pancreas and gradually induce hPSCs to enter β cells
.

Through systematic research, they adopted a phased approach to make β cells and found that 10 chemicals not only retained pancreatic progenitor cells in the 3D cell clusters, but also enhanced their resistance to NKX6.
1+/INS+ β cells Potential
.

In other words, the chemical combination enhances the clusters of 3D pancreatic progenitor cells derived from human pluripotent stem cells into functional β cells, and the differentiation rate of β cells can be as high as 80%
.

Ten chemical substances, namely LDN (BMP signaling inhibitor), T3 (thyroid hormone), RA, SANT1 (an inhibitor of sonic hedgehog signaling), Repsox (ALK5 inhibitor), ZnSO4, (2S,5S)-(E, E)-8-(5-(4-(trifluoromethyl)phenyl)-2,4-pentadienylamino)benzenelactam (TPB, a protein kinase C activator), EGF, NICO ( A vitamin B3) and gamma-aminobutyric acid (GABA, a neurotransmitter)
.

Another problem is that if undifferentiated cells remain in the mix, they may eventually become another kind of unwanted cells
.

In order to make cell-based treatments ultimately a viable option for patients, it is important to make these cells easier to manufacture, and researchers have found a way to optimize this process
.

Insulin (red) and NKX6.
1 (green) represent the two proteins produced by beta cells.
10 chemicals balance pancreatic progenitor cells in a 3D cluster.
In addition, they also observed how these cells grow in the laboratory
.

"Under normal circumstances, cells grow on plates, but we allow them to grow in three-dimensional space," said author Ronghui Li
.

Culturing cells in this way can create more shared surface area between cells and allow them to influence each other, just as they do during human development
.

After these cells were generated, they were transplanted into a mouse model of type 1 diabetes
.

The immune system of the model mice is modified so that it will not reject the transplanted human cells
.

It was found that within two weeks, the high blood sugar levels of these mice dropped to the normal range, and the β cells derived from the transplanted hPSCs had biological functions
.

Researchers will continue to study this technology in the laboratory to further optimize the production of beta cells
.

Before starting human clinical trials, more research is needed to assess safety issues
.

Reference: https:// Recommended reading: "Science Sub-Journal" Can't give up drinking and quitting? Ketogenic diet to assist! [Medical Week Video] Zhang Yukui, academician of the Chinese Academy of Sciences: The last century was the century of chemistry, and this century was the century of life sciences! [Nature] Three heavy articles in a row: Cancer stem cells in the intestine have adverse effects on neighboring cells [News] Talking about the status of molecular diagnostic technology details