Two studies investigate frontiers of islet cell transplantation for treating diabetes

Cell Transplantation Center of Excellence for Aging and Brain RepairFeb 18 2011

Two studies published in the current issue of Cell Transplantation (19:12) investigate frontiers of islet cell transplantation for treating diabetes. Researchers in Milan, Italy re-examine the role of bone marrow stem cells in diabetic therapy and islet cell regeneration and Canadian researchers offer improved strategies for optimizing pancreatic islet culture in vitro.

Both studies are in the current issue of Cell Transplantation, freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

The role of bone marrow (BM)-derived stem cells in the islet cell regeneration process continues to evolve. A team of Italian researchers reports that employing BM-derived stem cells as "feeder tissue," playing a protective role in supporting pancreatic islet repair for clinical use in treating diabetes, presents new therapeutic possibilities. Which cellular components of BM play the feeder role has not been clear.

"BM-derived cells have been found to differentiate into endothelial cells and their presence has been accompanied by a proliferation of recipient pancreatic cells that resulted in increased insulin production in the host pancreas," said corresponding author Dr. Lorenzo Piemonti.

The researchers speculate that BM plays a role as feeder tissue by modulating, or enhancing, vascularization.

"We recently demonstrated that pancreatic mensenchymal stromal cells (MSCs) originate from bone marrow cells," added Dr. Piemonti. "This suggests that there might be a 'cross talk' between bone marrow cells and the pancreas. Even more complex is the question of whether BM-pancreas cross talk plays a role in the pathogenesis of diabetes."

For the researchers, the 'easy availability' of BM, and that BM may offer "the ideal microenvironment for islet survival," suggest that exploring the possibility of using BM as the site for islet transplantation and they have started a clinical trial aimed at expanding on that idea.

"There is mounting evidence that BM and BM-derived stem cells can participate in the regeneration of pancreatic isolates," concluded Dr. Piemonti. "Future studies should evaluate their effect for the prevention and cure of diabetes should it be verifiable that there is a cross talk between BM and the pancreas."

Retrieving and preserving islet cells taken from nonliving donors for the purpose of islet cell transplantation to regenerate islet cells for patients suffering from diabetes is a current and successful practice. However, ensuring the integrity of the donor cells has been problematic.

"Following human islet isolation, apoptosis, or programmed cell death, occurs," said Dr. Maryam Tabrizian, member of a McGill University (Canada) research team. "Studies have shown that islet isolation exposes islets to a variety of stresses, including loss of vasculature and eventual hypoxia. These factors must be controlled to avoid cell death and the optimization of islet culture must be assured to prolong the survival and functionality of the cells in vitro."

According to the research team, nearly half of the islet mass is lost during donor surgery, preservation, transport and isolation, causing patients to undergo a second islet cell infusion. Better avenues of post-isolation culture, for up to two months duration, are needed, they said. This requires a better understanding of islet biology and the "basement membrane" of islet tissue. The researchers recommend combining many strategies supporting understanding of the need to maintain islet structural integrity and to provide a viable environment for islet preservation.

"Manipulation of the culture media, surface modified substrates, and the use of various techniques, such as encapsulation, embedding, scaffold and bioreactor approaches are among those strategies," concluded the researchers.

"The survival of islets after isolation remains a significant limiting factor in the field of islet transplantation." commented Dr. Rodolfo Alejandro, section editor for CELL TRANSPLANTATION and Professor of Medicine at the University of Miami Miller School of Medicine. The prevention and repair of islet damage during isolation is of paramount importance. These two studies discuss novel approaches for this problem.