Embryonic stem (ES) cells display the ability to differentiate in vitro into

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Homeostasis of blood glucose is mainly regulated by the coordinated secretion of glucagon and insulin from ␣-and ␤-cells within the islets of Langerhans. ] i signals in ␣-cells. These Ca 2؉ signals were synchronic among ␤-cells grouped in clusters within the islet, although they were not coordinated among the whole ␤-cell population. The response of ␣-cells was totally asynchronic. Therefore, both the ␣-and ␤-cell populations within human islets did not work as a syncitium in response to glucose. A deeper knowledge of ␣-and ␤-cell behavior within intact human islets is important to better understand the physiology of the human endocrine pancreas and may be useful to select high-quality islets for transplantation.

Cell therapy of diabetes mellitus has been mainly based on islet transplantation. Transplantation of pancreatic islet cells as a potential cure for diabetes has become a subject of intense interest and activity over the past two decades [1]. Islet transplantation involves isolation of islets and their transplantation through a simple injection into the umbilical vein, an operation devoid of the many potential complications of transplantating the pancreas [2]. Several barriers still delay, however, the success of this approach such as: (1) the diabetogenic effects of some immunosupressant agents [3]; (2) immunological rejection [4]; (3) the oncogenic effects of long-term immunosuppressive treatment and (4) insufficient number of beta cells transplanted [5]. A recent report has established that insulin-independence could be reached by combining a glucocorticoid-free immunosuppression with the transplantation of an adequate islet mass [6]. This successful example will increase the demand for human islets. Even with the new immunosuppressive therapy and less traumatic islet isolation procedures, which could be devised in the future, the shortage of donors is such that it will not be possible to meet the demand from all the patients with Type I (insulin-dependent) diabetes mellitus, however, consequently protocols to obtain insulin-secreting cells from other sources need to be developed. In this sense, the strategic knowledge Diabetologia (2001)