Studies evaluate transplantation potential and success of islet cells derived from pancreatic tissues

Two studies appearing in the current issue of Cell Transplantation (21:2/3), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/, evaluate the transplantation potential and success of islet cells derived from pancreatic tissues, in addition to a clinical study that reports the occurrence of adverse events.

Fresh islets are better than cultured islets

A team of researchers from Baylor Research Institute, Texas and the University Graduate School of Medicine in Okayama, Japan has found that islet cells freshly retrieved from the pancreas are superior to islet cells that have been cultured.

"Isolated islet cells deteriorate rapidly in culture," said study lead author Hirofumi Noguchi. "In our study we compared human fresh islet cells to cultured islets with in vitro and in vivo assays. Human islets, fresh and cultured, were transplanted into diabetic nude mice."

The researchers found that cultured islet yield decreased significantly after 24, 48 and 72 hours. The cultured islets showed a 24 percent loss after 48 hours. By comparison, the blood glucose levels of the diabetic mice were significantly lower with fresh islets after injection.

"Although islet culturing provides many benefits, such as quality testing and stability during travel time and treatment, we advocate avoiding culture time or, at least, curtailing culture time," said Dr. Noguchi. "In the future we will work to optimize the culture conditions to minimize islet loss."

Contact: Hirofumi Noguchi, MD, PhD, Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-chop, Okayama 700-8558, Japan.
Tel. +81-86-235-7257
Fax. +81-86-221-8775
Email [email protected]

Citation: Noguchi, H.; Naziruddin, B.; Jackson, A.; Shimoda, M.; Ikemoto, T.; Fujita, Y.; Chujo, D.; Takita, M.; Peng, H.; Sugimoto, K.; Itoh, T.; Kobayashi, N.; Onaca, N.; Levy, M. F.; Matsumoto, S. Fresh islets are more effective for islet transplantation than cultured islets. Cell Transplant. 21(2/3):517-523; 2012.

Comparing success of islet cells and kidneys both retrieved from non-heart-beating donors

When researchers in Japan compared the outcomes of islets isolated from non-heart-beating donors (NHBDs) with the patient outcomes of kidney transplantations using the kidneys retrieved from the same NHBDs, they found that isolated islets were more severely affected by the poor conditions of the deceased donors than were the kidneys transplanted from the same NHBDs.

"Grafts from non-heart-beating donors are used because of the limited availability of heart-beating, brain-dead donors," said study lead author Dr. Michihiro Maruyama of the Chiba-East National Hospital in Chiba City, Japan. "This study sought to determine whether the results of islet isolations were correlated with the clinical outcomes of kidney transplantations in cases where both grafts were harvested from the same NHBD."

When the authors cited the poor condition of the NHBDs, they also noted that, in Japan, islets are usually not harvested from heart-beating, brain-dead donors, so NHBD are the only source for islets.

They reported that, in general, patients receiving kidneys from NHBDs require prolonged hemodialysis. Their study showed that "good results of islet isolation predicted good clinical outcomes for kidney transplantation where the kidneys and pancreas were harvested from the same donor."

However, the results of islet isolation and outcomes of kidney transplantation were "discrepant."

The authors concluded that the results of islet isolation were more severely affected by the "marginal conditions of the NHBDs than were the functions of kidney transplantation."

"It is, therefore, difficult to predict the clinical outcomes of kidney trasplantation based on the results of islet isolation," the authors concluded.

Contact: Michihiro Maruyama, Department of Surgery, Chiba-east National Hospital, 673 Nitona, Chuo ku, Chiba City, Japan 2608712.
Tel. +81 43 261 5171
Fax. + 81 43 264 3269
Email [email protected]

Citation: Maruyama, M.; Kenmochi, T.; Saigo, K.; Naotake, A.; Iwashita, C.; Otsuki, K.; Ito, T. Results of islet isolation and their relationship to the clinical outcome of kidney transplantation in cases where both grafts are harvested from the same non-heart-beating donor. Cell Transplant. 21(2/3):559-563; 2012.

Adverse events in islet transplantation

While noting that "islet transplantation is one of the most promising therapies for unstable type 1 diabetes," researchers from the Baylor Research Institute report on the nature and severity of adverse effects nine patients encountered after a combined total of 17 islet transplants.

"The results of islet transplantation need to further improve to justify disadvantages," said study author Dr. Shinichi Matsumoto of the Baylor Research Institute Islet cell Laboratory.

According to the researchers, 16 severe adverse events (SAEs) and 12 less severe adverse events (AEs) occurred within the first year after transplantation. The grade three SAEs included elevated liver enzymes, hemorrhage, infection and renal dysfunction. The case of neutropenia was a grade four. Twelve of the 16 SAEs were likely related to the transplant protocols, they said, while five AEs were judged to be related to infusion procedures as they occurred within 10 days of islet infusion. Seven events occurring after 50 days were related to immunosuppresive therapy.

"Because more than half of the patients in this study experienced SAEs, improvements to both infusion procedures and immunosuppressive strategies to prevent SAEs are needed," said Dr. Matsumoto.

Contact: Shinichi Matsumoto, Baylor research Institute, Fort Worth Campus, Islet Cell Laboratory, 1400 8th Avenue, Fort Worth, Texas 76104.
Tel. 817-922-2570
Fax. 817-922-4645
Email [email protected]

Citation: Takita, M.; Matsumoto, S.; Noguchi, H.; Shimoda, M.; Ikemoto, T.; Chujo, D.; Tamura, Y.; Olsen, G. S.; Naziruddin, B.; Purcell, K.; Onaca, N.; Levy, M. F. Adverse Events in Clinical Islet Transplantation: One Institutional Experience. Cell Transplant. 21(2/3):547-551; 2012.

Source: Cell Transplantation Center of Excellence for Aging and Brain Repair