Insulin-secreting pancreatic islet cells have been generated from human spermatogonial stem cells (SSCs) directly isolated from human testicular tissue, researchers reported today at the American Association of Cell Biology 50th Annual Meeting in Philadelphia.
When grafted into diabetic mice that lacked a transplant-rejecting immune system, the bioengineered cells functioned much like somatic β-islet cells, the Georgetown University (GU) Medical Center researchers said.
By decreasing the animals' blood glucose levels, the human-derived islet cells demonstrated their potential to counter diabetic hyperglycemia in humans, added G. Ian Gallicano, Ph.D., who heads the GU research team.
Gallicano said that these results represent the first step of a transplant strategy to deliver β-islet cells that would not be rejected by the patient with type 1 diabetes because the stem cells would be obtained from the patient's own SSCs, the earliest precursors of male gamete sperm cells.
This transplant strategy would avoid the host-versus-graft issues that have plagued other transplant treatments for type 1 diabetes, Gallicano explained, because the SSCs would be obtained from male patients, modified in the laboratory to secrete insulin, and transplanted back to the donors.
Although surgeons currently transplant islet tissue from deceased donors into female and male patients with type 1 diabetes, this therapy is hampered by a woeful shortage of suitable donations and by complications resulting from host-versus-graft disease.
Gallicano said that obtaining beta-islet-like cells from the male patient's SSCs could solve the problem of immune rejection in males with type 1 diabetes, since the "treatment based on this research would be 'autologous,' that is, the cells come from the patient and would be recognized as 'self.'"
The fundamental approach of transforming male gametes into pluripotent stem cells might also be applicable to the female counterpart, oocytes, he added.
The β-islet-like cells were engineered from germ-derived pluripotent stem (gPS) cells produced from the SSCs. The engineered β-islet cells secreted insulin and exhibited many of the markers characteristic of normal islet cells including C-peptide (pro-insulin) production and the expression of PDX1, a transcription factor involved in pancreatic development.
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Georgetown University contacts:
Ian Gallicano, Ph.D.
Georgetown University Medical Center
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Gallicano will present "Functional, insulin-secreting pancreatic endoderm derived from human spermatogonial stem cells," Sunday, Dec. 12, 2010, 11:30 a.m. to 1 p.m., Metabolic Diseases 1. Exhibit Halls A/B/C, Program 703, Board B1113
Co-Authors:
Anirudh Saraswathula(1); Shenglin Chen, Asif Zakaria, and G. Ian Gallicano(2)
1Biotechnology and Life Sciences Laboratory, Science and Technology Division, Thomas Jefferson High School for Science and Technology, Alexandria, VA.
2Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC