OBJECTIVES: Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested. MATERIALS AND METHODS: Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days. RESULTS: At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy. CONCLUSIONS: Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.
OBJECTIVES: Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested. MATERIALS AND METHODS: Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days. RESULTS: At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabeticrats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy. CONCLUSIONS: Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.
Authors: Mahmoud M Gabr; Mahmoud M Zakaria; Ayman F Refaie; Amani M Ismail; Mona A Abou-El-Mahasen; Sylvia A Ashamallah; Sherry M Khater; Sawsan M El-Halawani; Rana Y Ibrahim; Gan Shu Uin; Malgorzata Kloc; Roy Y Calne; Mohamed A Ghoneim Journal: Cell Transplant Date: 2012-06-15 Impact factor: 4.064
Authors: Giuseppe Orlando; Kathryn J Wood; Paolo De Coppi; Pedro M Baptista; Kyle W Binder; Khalil N Bitar; Christopher Breuer; Luke Burnett; George Christ; Alan Farney; Marina Figliuzzi; James H Holmes; Kenneth Koch; Paolo Macchiarini; Sayed-Hadi Mirmalek Sani; Emmanuel Opara; Andrea Remuzzi; Jeffrey Rogers; Justin M Saul; Dror Seliktar; Keren Shapira-Schweitzer; Tom Smith; Daniel Solomon; Mark Van Dyke; James J Yoo; Yuanyuan Zhang; Anthony Atala; Robert J Stratta; Shay Soker Journal: Ann Surg Date: 2012-05 Impact factor: 12.969
Authors: Giuseppe Orlando; Pedro Baptista; Martin Birchall; Paolo De Coppi; Alan Farney; Nadia K Guimaraes-Souza; Emmanuel Opara; Jeffrey Rogers; Dror Seliktar; Keren Shapira-Schweitzer; Robert J Stratta; Anthony Atala; Kathryn J Wood; Shay Soker Journal: Transpl Int Date: 2010-11-10 Impact factor: 3.782