Diabetes mellitus is a metabolic disorder that affects millions of people. In both Type 1 and 2 diabetes, insufficient numbers of insulin-producing beta-cells are a major cause of defective control of blood glucose and its complications. Of course, we know that islet transplantation has been considered to be a first line therapeutic option for the treatment of diabetes based on the innovative success of the Edmonton protocol. However, a serious shortage of donor pancreata is a critical problem unfortunately. To overcome the issues and to achieve the ultimate goal of curing diabetes, new approaches, such as stem cell research and cell-based therapy, have been researched and developed. We suggest that the following issues should be solved in order to realize cell-based therapy. The first is to establish a source of stem/progenitor cells that will multiply easily in vitro and maintain their property as progenitor cells, and the second, the most difficult and as yet unsolved, is how to differentiate these cells and acquire fully functional islets. Multiple groups including us have developed successful in-vitro protocols to differentiate human embryonic stem cells and somatic stem cells into progenitors capable of insulin production and glucose-stimulated insulin secretion. Protocols for the in vitro differentiation of embryonic stem (ES) cells based on normal developmental cues have generated beta-like cells that produce high levels of insulin, albeit at low efficiency and without full responsiveness to extracellular levels of glucose. Induced pluripotent stem (iPS) cells also can yield insulin-producing cells following similar approaches. Major hurdles that must be overcome to enable the broad clinical translation of these advances include teratoma formation due to contamination of undifferentiated ES or iPS cells, and the need for immunosuppressive drugs. Generation of autologous iPS cells should prevent transplant rejection, but may prove prohibitively expensive. Banking strategies to identify small numbers of stem cell lines homozygous for major histocompatibility loci have been proposed to enable beneficial genetic matching that would decrease the need for immunosuppression. Classes of stem cells that can be expanded extensively in culture but do not form teratomas, such as bone marrow-derived mesenchymal stem cells and adipose tissue-derived mesenchymal stem cells, offer possible alternatives for the production of beta-like cells, but further evidence is required to document this potential. Although remarkable progress has been made in differentiating stem cells into insulin-producing cells, there is still more research needed to produce a fully functional adult beta cell. In this chapter, we review progress towards the goal of utilizing stem cells for cell therapy for diabetes.
|ホスト出版物のタイトル||Encyclopedia of Cell Biology Research|
|出版社||Nova Science Publishers, Inc.|
|出版ステータス||Published - 01-03-2012|
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