Generation of Functional Human Pancreatic β Cells In Vitro

Harvard Stem Cell Institute, developmental biologist Douglas Melton and his colleagues report in the journal Cell this week, and a formula can put human stem cells into functional pancreatic β cells – the cells can be type 1 diabetes own immune system damage.


Transplanted into diabetic mice after two weeks in the laboratory-generated human pancreatic β cells secrete enough insulin (green) to heal animals. (Source: Douglas Melton)

Douglas Melton than anyone eager to get a cure for diabetes, because his son was a baby when suffering from the disease, while his daughter was diagnosed with the disease at age 14. In the past 20 years, most of the time, the Harvard Stem Cell Institute, developmental biologist Douglas Melton has been his research focused on the discovery of a cure for the disease. He and his colleagues reported in this week’s closer to this goal important step: a recipe can put human stem cells into functional pancreatic β cells – the cells can be type 1 diabetes (such as Melton’s son and daughter )’s own immune system damage. The researchers in this study changes in the islet β cells to glucose by producing insulin to react as normal β cells do. When injected into the mouse forms of diabetes, the cells can be cured of the disease.

“Diabetes research community for this type of breakthroughs have been waiting for a long period of time,” Imperial College London study β cell genetic Jorge Ferrer said. This laboratory-generated cells may become a valuable tool for the study of diabetes, and Melton hopes that it can eventually be used to treat patients.

The whole day, the pancreas in regulating the body’s blood sugar levels by secreting insulin on postprandial glucose increase react, which helps cells absorb sugars. In patients with type 1 diabetes, the immune system mistakes its own kill β cells, and the reason is not yet clear, and the body can not live without insulin. People through carefully calibrated doses of insulin injections to control their diabetes. However, this is precisely obtained from a healthy pancreas insulin control is almost impossible to match, so the researchers hoped for decades to find a way to replace the lost cells.

When scientists isolated human embryonic stem cells (ES cells) in 1998, the hopes soared. ES cells are pluripotent, which means that in theory, they can be converted into any cell of the body, including the β cells. In fact, one of the first studies researchers is trying to use ES cells to produce islet β cells. Later, they attempt to use a so-called induced pluripotent stem cells (iPS cells), by reprogramming somatic cells into embryonic-like state. Either way, “This proved to be a very complex task,” Nashville’s Vanderbilt University study Magna pancreas development Mark Johnson said.

Several research teams have the stem cells to differentiate into precursor cells, β, when placed in experimental animals when mature. However, these cells need six weeks to fully become a functional β cells, and they are not readily available in vitro studies. However, clinical trials have begun to test their efficacy in the month to a patient.fx1

On this week’s journal Cell, Melton and his colleagues reported a complex formula, which can be either direct human embryonic stem cells (ES cells) or iPS cells into functional β cells. This breakthrough is completed on the basis of Melton laboratory dedicated more than a decade working on. He and his colleagues studied the regulation of pancreatic development painstaking signals and other applications of their discovery, developed a method of stem cells to differentiate into mature β cells. “There is not magic,” Melton said. “It is not even used in developmental biology of a discovery.”

“The draft is repeatable, but more tedious,” Melton added. Stem cells grown in a flask requires five different molecular species of growth medium and 11 factors from the protein to the carbohydrate, add it to the exact needs of more than 35 combinations of them can be converted into a genius β cells. From a good hand, Melton Road, the technology can produce 200 million β cells in a 500 ml flask – in theory, enough to treat a patient. Melton said that the draft seems to work with the ES and iPS cell lines are equal.

Before the cells can be used to treat type 1 diabetes, researchers need to find a way to protect them from immune rejection. The same trigger the disease may be an autoimmune response attacks the new β cells from iPS cells derived from the patient’s own, and the normal immune response will destroy the β-derived ES cells, which appears to be heterogeneous. (This has been trying to use a challenge from deceased organ donors β cell transplant to treat type 1 diabetes.) Melton and his colleagues are exploring how stem cell-derived β cells into the capsule, and how modified β cells, enabling them to resist immune attack.

At the same time, the cells may contribute to autoimmune disease. “This technology may provide some way to create a model system to study the genetic basis of diabetes, or the discovery of new treatments to improve the existing β cells ,,” Ferrer said. Melton said his lab has come from diabetes (type 1 and type 2, and β cells are not destroyed) and healthy control group iPS cell lines. They generate β cell lines from those cells, may explain how to find the differences between the different forms of the development of diabetes. They will also filter out chemicals, which can prevent and even reverse diabetes damage to β cells.

Melton said his son and daughter – now 23 and 27 years old, on the progress made by his research team was very happy, but surprised. Reversing the roles of father and son, they gently nagging him “started to address [immune rejection] problems.”

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