Stem cells and regenerative medicine for diabetes mellitus.
A profound knowledge of the development and differentiation of pancreatic tissues, especially islets of Langerhans, is necessary for developing regenerative therapy for severe diabetes mellitus. A recent developmental study showed that PTF-1a is expressed in almost all parts of pancreatic tissues, in addition to PDX-1, a well-known transcription factor that is essential for pancreas development. Another study suggested that alpha cells and beta cells individually, but not sequentially, differentiated from neurogenin-3--expressing precursor cells. Under strong induction of pancreas regeneration, it is likely that pancreatic duct cells dedifferentiate to grow, express PDX-1, and re-differentiate toward other cell types including islet cells. Duct epithelium-like cells can be cultivated from crude pancreatic exocrine cells and can be induced to differentiate toward islet-like cell clusters under some culture conditions. These cell clusters made from murine pancreas have been shown to control hyperglycemia when transplanted into diabetic mice. Liver-derived oval cells and their putative precursor H-CFU-C have been shown to differentiate toward pancreatic cells. Furthermore, extrapancreatic cells contained in bone marrow and amniotic membrane are reported to become insulin-producing cells. However, their exact characterization and relationship between these cell types remain to be elucidated. Our recent study has shown that islet-like cell clusters can be differentiated from mouse embryonic stem cells. Transplantation of these clusters could ameliorate hyperglycemia of STZ-induced diabetic mice without forming teratomas. Interestingly, these cells expressed several genes specific to exocrine pancreatic tissue in addition to islet-related genes, suggesting that stable and efficient differentiation toward certain tissues can only be achieved through a process mimicking normal development of the tissue. Perhaps recent developments in these fields may rapidly lead to an established regenerative therapy for diabetes mellitus.
Sumi
Shoichiro
S
Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. sumi@frontier.kyoto-u.ac.jp
Gu
Yuanjun
Y
Hiura
Akihito
A
Inoue
Kazutomo
K
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D006224:Cricetinae; D003920:Diabetes Mellitus / Q000601:surgery*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D012038:Regeneration; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000502:physiology
D015415:Biomarkers; D014157:Transcription Factors