Diabetes researchers are developing treatments for type 1 diabetes by transplanting insulin-producing islet cells from a donor pancreas into patients whose islet cells have been destroyed. Now City of Hope researchers report a method that could make these kinds of therapies available to more patients, freeing them from lifelong, daily insulin injections.
Adult stem cells from human bone marrow can mature into cells resembling islet cells when seeded into human pancreas tissues, according to Chu-Chih Shih, Ph.D., assistant professor in the Division of Hematology & Hematopoietic Cell Transplantation, and colleagues. These cells could potentially be used as replacement therapy for type 1 diabetes. The study appeared in the journal Stem Cells and Development in October.
City of Hope is one of 10 National Institutes of Health-designated national islet cell transplantation centers, and one of 14 designated by the Juvenile Diabetes Research Foundation. Through the center, physicians retrieve islet cells for transplant from donor cadavers. “There have been only 2,000 pancreatic donors, but there are millions of patients with diabetes,” said Shih. “Stem cell therapies could supply alternative sources of cells that can differentiate into pancreatic islet cells, which would benefit most patients with diabetes.”
Collaborating with Stephen Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and clinical director of the Division of Cancer Immunotherapeutics & Tumor Immunology, and Ivan Todorov, Ph.D., associate research scientist in the Department of Diabetes, Endocrinology & Metabolism, Shih began to explore whether a type of human bone marrow cells could form islet-like cells.
The researchers first labeled stem cells with a green tracer dye and then injected them into transplanted human pancreas tissue carried on a laboratory mouse called the SCID-Hu mouse.
“Four months later we harvested tissue and saw green cells, meaning that the stem cells survived,” said Shih. “But the important question was, did they produce insulin?”
Not only did they do that, but they also pumped out insulin in proportion to the amount of the blood sugar glucose they were exposed to.
That encouraged researchers, because one of the problems when patients must inject insulin is getting the proper dose into the body.
Insulin is the hormone that signals cells to absorb glucose: The more glucose in the bloodstream, the more insulin is needed. This experiment shows that the islet-like stem cells respond to glucose much like normal islet cells do.
The group also reported another remarkable finding: When they transplanted these cells into laboratory mice engineered to have type 1 diabetes, the transplant largely relieved mice of diabetic symptoms.
“Basically this experiment proves that the green islets derived from the stem cell graft are physiologically functional — that they are as good as the islets you would purify from the pancreas,” said Shih.
Todorov agrees that this is critical evidence that bone marrow-derived stem cells can mature into insulin-producing cells but cautions that researchers are probably about five years away from trying these kinds of therapies in humans. “I believe that stem cell replacement in diabetes will be a reality,” he said, “and that the source of those cells will be either bone marrow, pancreas or embryonic stem cells.”
The experiments provide convincing evidence that cells from bone marrow are good candidates for regeneration therapies, Shih said. “This study shows that putting stem cells in the pancreas provides them with the right environment for them to grow and develop.”
Cuiwei Ai, Ph.D., a former postdoctoral researcher in Shih’s lab, was the paper’s lead author. Marilyn Slovak, Ph.D., professor of pathology and director of the Section of Cytogenetics, and David DiGiusto, Ph.D., director of hematopoietic cell therapies in the Division of Hematology & Hematopoietic Cell Transplantation, also contributed to the study.
The National Institutes of Health, the Ella Fitzgerald Charitable Foundation, the California Community Foundation and the Rosalinde and Arthur Gilbert Foundation funded the research.
Of the more than 20.8 million people with diabetes in the United States, 5 to 10 percent have type 1. Although it can develop at any age, type 1 diabetes most commonly appears in children and young adults. One in every 400 to 600 children has the disease.