Commentary by: Kathryn Cogger, PhD
Researchers discussed the latest advances in cell replacement therapy for the treatment of type 1 diabetes in the January issue of Endocrinology.
While insulin is the mainstay of treatment for type 1 diabetes, insulin is limited in that it does not eliminate the risk for long-term complications of diabetes and often causes fluctuations between hypoglycemic and hyperglycemic states. Thus, research has focused on alternative therapies that offer the potential for improved glycemic control and prevention of long-term complications. To date, the best progress has been made with islet transplantation, xenotransplantation, and the generation of human embryonic stem cell (ESC) (hESC)- or human-induced pluripotent stem cell (hiPSC)-derived β-cells.
“Islet transplantation is already being used as a treatment option in certain specialized centers, and in conjunction with immunosuppressive protocols, has excellent 5-year outcomes,” explained coauthor of the review article Kathryn Cogger, PhD, Postdoctoral Research Fellow, McEwen Centre for Regenerative Medicine, University Health Network, Toronto.
This treatment is “limited in it’s mainstream application due to a lack of islet donors, and the need for life-long immunosuppression,” Dr. Cogger said.
“Xenotransplantation studies have reached the clinical trial stage, with no signs of retroviral or microorganism transmission to the patients, and improvements in hypoglycemic awareness,” Dr. Cogger said. “Living Cell Technologies currently has 2 clinical trials underway, using islets from pathogen-free pigs, encapsulated in alginate microcapsules. We are awaiting the results of their trial completed in 2013,” Dr. Cogger added.
Human Pluripotent Stem Cell-Derived β-Cells
“At the end of last year (2014), 2 groups published reports on generating monohormonal, insulin-producing cells from stem cells in vitro, which could successfully reverse diabetes in a mouse model. This was a major breakthrough in the field, as up until this point, most insulin-expressing cells generated in vitro were polyhormonal, and unresponsive to glucose stimulation,” Dr. Cogger said.
“The regenerative medicine company ViaCyte, recently received FDA approval to commence a clinical trial using a device containing stem cell-derived pancreatic endoderm cells,” Dr. Cogger said. “Specifically, this is the first time where a human embryonic stem cell-based device is transplanted into a diabetic patient,” she noted.
The phase 1/2 clinical trial began in September 2014 at the University of California, San Diego, and is expected to enroll approximately 40 patients. In October 2014, the company announced the first successful implantation of the product in a patient with type 1 diabetes.
“The company also received clearance from Health Canada to expand the trial internationally,” Dr. Cogger said.
“We have reported in 2 publications successful maturation and function of human embryonic stem cell-derived pancreatic precursor cells in macro-encapsulation device,” commented Timothy Kieffer, PhD, Professor, Department of Cellular and Physiological Sciences and the Department of Surgery, University of British Columbia, British Columbia, Canada. “I believe these findings are encouraging, and support the approach being tested clinically by ViaCyte,” Dr. Kieffer said.
“For the progression of both xenotransplantation and stem cell-derived β-like cell therapies, encapsulation technology is the area of focus,” Dr. Cogger said. “Creating a device that can contain large numbers of cells, providing them with sufficient oxygen and nutrient supply, whilst allowing efficient monitoring of blood glucose levels, and secretion of insulin as needed, is one of the main obstacles in progression of these therapies to the clinic,” Dr. Cogger said. “There are also still refinements to be made in the protocol for generating β-like cells from stem cells in vitro, including addressing ways to produce these cells on a large scale,” Dr. Cogger noted.
February 13, 2015
Cogger K, Nostro MC. Recent advances in cell replacement therapies for the treatment of type 1 diabetes. Endocrinology. 2015;1(1):8-15.
Pagliuca FW, Millman JR, Gürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014;159(2):428-439.
Rezania A, Bruin JE, Arora P, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014;32(11):1121-1133.
ViaCyte. ViaCyte’s VC-01™ Investigational Stem Cell-Derived Islet Replacement Therapy Successfully Implanted into First Patient. Available at: http://viacyte.com/press-releases/viacytes-vc-01-investigational-stem-cell-derived-islet-replacement-therapy-successfully-implanted-into-first-patient/. Accessed February 13, 2015.
ViaCyte Receives Clearance from Health Canada for Diabetes Clinical Trial. Available at: http://viacyte.com/press-releases/viacyte-receives-clearance-from-health-canada-for-diabetes-clinical-trial/. Accessed February 13, 2015.
Bruin JE, Rezania A, Xu J, et al. Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice. Diabetologia. 2013;56(9):1987-1998.