Using sperm stem cells to make pancreatic beta insulin-producing cells could one day form the basis of a safe treatment for type 1 diabetes in men with the disease, and there is no reason why a similar treatment based on egg stem cells should not be feasible for women with the disease, scientists told a conference in the US on Sunday.
Dr G. Ian Gallicano, an associate professor in the Department of Cell Biology and director of the Transgenic Core Facility at Georgetown University Medical Center (GUMC) in Washington DC told delegates at the 50th Annual Meeting of American Society for Cell Biology in Philadelphia, that their lab and animal study was “proof of principle” that it was possible to extract human spermatogonial stem cells (SSCs) from testicular tissue and “morph” them into insulin-secreting beta islet cells normally found in the pancreas.
Moreover, he and his team found it was possible to do this without having to insert the extra genes most labs use to turn adult stem cells in a tissue of choice.
“No stem cells, adult or embryonic, have been induced to secrete enough insulin yet to cure diabetes in humans, but we know SSCs have the potential to do what we want them to do, and we know how to improve their yield,” said Gallicano.
He and his team are hopeful that their study means men with type 1 diabetes may be able to grow their own insulin-producing beta-islet cells from their testicular tissue.
They stressed that while the study was “male-centric”, there is no reason why this new method of differentiating and grafting beta-islet cells should not also work with the female equivalent, the oocyte cells that go on to become mature eggs in the ovaries.
Beta-islet cells are the cells in the pancreas that produce insulin. People with type 1 diabetes mellitus, sometimes referred to as juvenile or early onset diabetes, don’t have enough of these cells because their immune system destroys them, resulting in too much glucose in their blood and urine.
Diabetes is one of the most serious health problems in the US today, affecting around 8 per cent of the population, or about 23.6 million Americans.
However, over the last thirty or forty years, treatment for diabetes has not changed much, and is still dependent on blood tests to determine glucose levels and then controlling them with insulin supplements.
Also, while new treatments, such as transplanting beta-islet cells, have emerged in recent years, they carry the risk of rejection, and even though scientists have cured diabetes in mice using adult stem cells genetically reprogrammed to behave like embryonic stem cells (the so-called induced pluripotent stem or IPS cells), these can cause problems, such as trigger tumors in the transfected tissue, said Gallicano.
So instead of trying to improve the IPS method, he and his team turned to another source of readily available stem cells, the SSCs that are the only precursors to sperm cells in men.
Gallicano explained that SSCs “are male germ cells as well as adult stem cells”, so they don’t need to be reprogrammed with extra inserted genes to become embryonic stem cells.
“We found that once you take these cells out of the testes niche, they get confused, and will form all three germ layers within several weeks,” said Gallicano:
“These are true, pluripotent stem cells,” he added.
For their study, they used SSCs from deceased donors and worked with them in “test tubes” and also in live mice bred to have type 1 diabetes.
From 1 gram of testicular tissue they were able to produce about 1 million stem cells and found they showed many of the biomarkers characteristic of normal beta-islet cells: they produced C-peptide (pro-insulin), expressed PDX1, a transcription factor involved in pancreatic development, and behaved very much like somatic beta-islet cells.
And most significantly, when they transplanted the cells into the backs of the immune-deficient diabetic mice, they found they decreased the glucose levels for about a week, showing that the cells were making enough insulin to reduce hyperglycemia.
Gallicano said that while their study shows the effect only lasted a week, they have since then successfully increased the yield substantially.
Also, he and his colleagues said treatment based on their research could use cells taken from the patient’s own testicular tissue, so the immune system would recognize the cells as “self” and not attack them, thus removing the risk of rejection.
Gallicano and his co-researchers reported having no personal financial interests in the study, which was paid for by a grant from GUMC and funds from the American Diabetes Association, patient contributions to the GUMC Office of Advancement, and a GUMC diabetes specialist, Dr Stephen Clement.
“Functional, insulin-secreting pancreatic endoderm derived from human spermatogonial stem cells.”
A. Saraswathula, S. Yamaguchi, A. Zakaria1, Gallicano.
Presented Sunday 12 December 2010 at the American Society for Cell Biology 50th Annual Meeting, Philadelphia.
Abstract ID# 703/B1113
Additional source: Georgetown University Medical Center press release.
Written by: Catharine Paddock, PhD