Cell therapies for type 1 diabetes mellitus.
Type 1 diabetes is caused by autoimmune destruction of pancreatic beta-cells and is characterised by absolute insulin insufficiency. The monocellular nature of this disease and endocrine action of insulin make this disease an excellent candidate for cellular therapy. Furthermore, precedent for cellular therapies has been set by successful cadaveric whole pancreas and islet transplantation. In order to expand the supply of cells to meet current and future needs, several novel cell sources have been proposed, including human beta-cells or islets expanded in culture, islet xenografts and pancreatic ductal progenitor cells. Surrogate beta-cells derived from hepatocytes, intestinal K cells or non-endodermal cell types have also been suggested. Stem cells found in bone marrow and umbilical cord blood have been used extensively to repopulate the haematopoietic system and offer the possibility of autologous transplantation. Recent studies have suggested that these stem cells may also have a broader capacity to differentiate, possibly into beta-cells. Stem cells from embryonic sources, such as human embryonic stem and embryonic germ cells, have the ability to proliferate extensively in culture and have an inherent developmental plasticity that may make them a potentially unlimited source of cells that can sense glucose and produce mature insulin. The wide range of proposed cell sources and our increasingly clear picture of pancreatic development suggest that novel cellular therapies might one day compete with non-cellular glucose sensing and insulin delivery devices.
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 733 N. Broadway, BRB 769, Baltimore, MD 21205, USA. mshambl1@jhmi.edu
Michael J
MJ
Shamblott
Gregory O
GO
Clark
D000818:Animals; D017690:Cell Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D016381:Islets of Langerhans Transplantation; D016035:Pancreas Transplantation; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous