Using stem cells to make pancreatic beta cells

Human Body is likely to attack its own cell, genetically in a condition called Type 1 Diabetes. In diabetes, body destroys beta cells in pancreas that make insulin. Insulin is important to body because it helps to convert sugar into energy. This disorder can occur at any age. Therefore, if not treated carefully with insulin shots or pump it can be fatal. Xiaojun Lance Lian, associate professor of biomedical engineering and biology at Penn State, has provided a new approach for its treatment. According to him, using stem cells to make beta cells can help to cure this disease. “If we could convert stem cells into pancreatic beta cells and transfer them back to the patient, it might be possible to cure diabetes,” Lian said.

For the first time, Lian and his colleges used human stem cells to make pancreatic beta cells. Beta cells are capable of producing insulin using only small molecules in vitro. Hence, making the process economical and efficient. “Diabetes is a severe disease in the United States and around the world,” Lian said. “The patient’s own immune cells kill their ability to produce insulin and regulate their glucose levels. We thought stem cells could potentially solve the problem and allow a person to regulate their insulin and glucose levels appropriately again.” Stem cells can become any other type of cell by environmental signals and some mature cells can even revert to stem cells (induce pluripotent).

Pancreatic Beta Cells from Stem cells:

Researchers found that this process worked for human embryonic and induced pluripotent stem cells. Both are derived from federally approved stem cells lines. The efficiency of their method could decrease the need for human embryonic stem cells in future according to Lian. Accordingly, stem cells can grow into any cell type through environmental conditions or laboratory interference. Hence by using this trick they are finding out condition to sway a stem cell to develop into a desired cell type. So, according to Lian, “Scientists have been trying to find the solution for more than 20 years. Our lab realized we had to take a different approach.”

Researches are using stem cells to make insulin-producing pancreatic beta cells.
Stem cells to produce pancreatic beta cells.

In earlier trails, scientist used growth factors or proteins to change stem cells into different types. However, growth factors are costly and unstable to use. Therefore, they made use of small organic molecules than large ones. Lian said, “We could still emulate the effect of the growth factors to differentiate stem cells to an intermediate stage.” The small molecule contains CHIR99021 (CHIR) a chemical compound and signaling pathway called Wnt that directs cell to one of the intermediate types. “No one else discovered this because you have to precisely and carefully optimize the CHIR concentration,” said first author Yuqian Jian a student in Lian’s lab.

CHIR is very important for stem cell differentiation. Lian and his team tested all possible concentrations and found one for converting stem cells into endoderm cells. The lower does was not enough and the higher ones killed the cells. Finally at 2nd and 3rd lowest doses, almost 87% of stem cells turned into endoderm cells. These endoderm cells could be guided to develop into pancreatic beta cells.

Further Considerations

Researchers also tested the developed pancreatic beta cells with glucose. Lian explained that these cells produced insulin based on glucose in surrounding, showing their capabilities. To prevent patients’ bodies from killing these cells, researchers plan to enclose the engineered stem-cell derived beta cells with biomaterial polymers before transplanting. So, this will protect the cells. Also letting them to observe their surrounding to make appropriate levels of insulin.

“Our approach allows us to use the same low-cost chemical at different doses to generate different intermediate cell types, one of which can become pancreatic beta cells,” Lian said. “We’re now working to optimize this approach and move it to clinical trials, but we’ve done the hard work of significantly lowering the cost. Cell therapy is amazing, but not everybody can afford it. Our goal is to make it available to everyone who needs it.”