The first success in turning bone marrow cells into pancreatic cells strengthens the hypothesis that adult stem cells can change their purpose
The tremendous potential inherent in stem cells places them at the forefront of biological research. The research focuses on the embryonic stem cells - cells that are produced from embryos in the first stages of development and have not yet acquired their final function. At this stage they can develop into all types of cells in the body. The flexibility of embryonic stem cells raises the hope that it will be possible to use them to create new tissues or restore damaged tissues. Scientists predict that in the future, embryonic stem cells that will differentiate into pancreatic cells will be used to cure diabetes and stem cells that will differentiate into nerve cells will be used to cure Alzheimer's, Parkinson's and multiple sclerosis.
In order to direct the differentiation of the embryonic stem cells, they must be exposed to the appropriate signals, isolate from the cell culture those that have acquired the desired function and multiply them. Scientists are now studying all these procedures. However, even after they succeed in isolating and multiplying the desired stem cells, it will still be necessary to overcome the body's rejection reaction when they are transplanted into patients.
At the same time as research on embryonic stem cells, intensive research is being conducted on adult stem cells - cells that are found in every tissue in the body and from which all tissue cells develop. Unlike the embryonic stem cells, these cells have already acquired their unique identity and are used in the tissue as an emergency reserve. In recent years it has become clear that the adult stem cells, even though they have already acquired their final function, can return to the embryonic state and get a new identity when they are transferred from the mother tissue to another tissue. According to the researchers' assessment, the cells with the greatest potential are mature stem cells from the bone marrow that can, at least theoretically, become muscle, skin, heart, kidney, pancreas, liver and nerve cells.
The functional flexibility of the adult stem cells gives them tremendous potential: it allows using the patient's own adult stem cells and transferring them from tissue to tissue in his body without the risk of rejection. But beyond that, the discovery led to a conceptual revolution in biological thinking. One of the cornerstones of developmental biology was the knowledge that a cell that acquired a defined role during embryonic development cannot change it. And here it turned out that the process is reversible: cells of one type can, under changing circumstances, become cells of another type.
But in the last four years, doubts began to arise. Articles appeared in the leading journals claiming that it was difficult to repeat the results of the experiments in which the flexibility of the adult stem cells was demonstrated. It turned out that in many cases the cells "wayed" the researchers: some of them underwent mutations that gave them new roles; Other cells "stole" a piece of DNA from the tissue in which they were implanted and functioned with it as if they had changed their identity. And a year ago it became clear that in many cases the new programming of the cells is nothing but a connection of the transplanted cells with existing cells in the tissue.
Stem cell researchers are currently divided into two camps: those who are convinced that adult stem cells are capable of changing their identity, and those who completely reject this possibility. In a study published last Friday in the "Investigation" Journal of Clinical, a team of researchers from the New York University School of Medicine was able to demonstrate the functional flexibility of adult stem cells. The researchers showed for the first time that stem cells from the bone marrow of mice can function as insulin-secreting cells when transplanted into the pancreas.
One of the hopes planted in the stem cells is to cure diabetes. In diabetes, the secretion of insulin is impaired by cells in the pancreas called beta cells. Diabetes has two forms: in type 1 diabetes, the body's immune system inadvertently attacks beta cells and destroys them; In type 2 diabetes, which is sometimes associated with obesity, beta cells lose (partially or completely) the ability to secrete insulin. The results of experiments in animals and recently also in humans show that beta cell transplantation in the pancreas may contribute to curing both types of diabetes. However, due to a lack of donors and due to the severe side effects of the drugs that are supposed to help prevent transplant rejection, beta cell transplantation is not done to the extent necessary. Adult stem cells are therefore natural candidates for this purpose.
The researchers from New York, led by Mahbub Hossein, transplanted stem cells from the bone marrow into the pancreas of mice. To make sure that the cells were indeed taken up by the pancreas, changed their identity and became pancreatic cells, the researchers used two tricks: they transplanted bone marrow cells from male mice into the pancreas of mice. Thus, by tracing the Y chromosome that characterizes the male cells, they were able to identify the pancreatic cells that originated from the male bone marrow cells. In addition, they injected into the transplanted cells a gene that codes for a fluorescent substance, which began to glow when the gene responsible for insulin production came into action. If cells are found in the pancreas that contain a Y chromosome and glow with fluorescent light, the researchers will know that these are bone marrow cells that have changed their identity, turned into pancreatic cells and started to secrete insulin.
One month after the start of the experiment, the researchers checked the identity of the cells in the pancreas of the mice. It turned out that about 3% of the beta cells in the pancreas were transplanted bone marrow cells that produced insulin. The researchers note that there were bone marrow cells of male origin that escaped from the pancreas of the mice, but only the cells in the pancreas produced insulin. According to them, "these results indicate that cells derived from bone marrow cells can activate the gene that produces insulin only in the pancreas."
Is there conclusive proof of the flexibility of mature stem cells from the bone marrow?
"The flexibility of adult stem cells is still controversial," says Prof. Nissim Benvanisti from the Institute of Life Sciences at the Hebrew University, one of the leading stem cell researchers in the world. "The research that has just been published is another layer to the approach that claims that flexibility is indeed possible, but it is still too early to change the textbooks in biology."
