All Stem Cells Japan

Introduction
Diabetes mellitus (DM), which causes about 5% of all deaths globally each year (http://www.who.int/en), afflicts 246 million people worldwide presently and will affect 380 million by 2025. DM consists of two diseases, type 1 and type 2, with distinct etiology. Type 1 DM, which accounts for 5%–10% of all DM cases, is caused by autoimmune destruction of the pancreatic β-cells, resulting in a reduction of insulin production. In contrast, type 2 DM is initially caused by insulin resistance and later progresses to β-cell dysfunction that also results in a reduction of insulin production [2,3]. Initial treatment for type 2 DM is usually a combination of diet, exercise, and drugs that stimulate insulin secretion from β-cells, reduce hepatic glucose output, or increase insulin sensitivity in target cells. However, as the disease progresses further, β-cell mass decreases (due to increased apoptosis and reduced neogenesis/replication); these treatments become insufficient to achieve or sustain the desired blood glucose level. Therefore, the majority of type 2 diabetic patients will require insulin therapy, typically between 5 and 10 years after the initial diagnosis.
It is well established that the risk of diabetic complications is dependent on the degree of glycemic control in diabetic patients. However, while aggressive insulin therapy that maintains glucose levels near the normal range reduces the risk of secondary complications, patients often find such control difficult to achieve and suffer an increased risk of hypoglycemia. This is due to the fact that external insulin injection cannot mimic the physiological control that pancreatic β-cell-derived insulin secretion exerts on the body's glycemia. In contrast, replacement of a patient's islets of Langerhans by whole pancreas transplantation or by islet transplantation is the only treatment capable of achieving normoglycemia. However, due to the scarcity of donor pancreases and the necessity of patients undergoing lifelong immunosuppression, this therapy can be afforded to only a limited number of patients. Thus, a renewable source of a physiologically competent substitute for primary human pancreatic islets is highly desirable.
Many alternative strategies have been considered for the replacement of damaged β-cells, including the use of pancreatic β-cell lines, regenerating native islet cells, embryonic stem cells (ESC), and bone marrow stem cells (BMSC). Through the manipulation of culture conditions, BMSC have been shown to produce low levels of insulin [10–13]. However, the low-level insulin production and the unlikelihood of reproducing the culture conditions in vivo make this approach unfit for clinical applications. To overcome these shortcomings, Li et al. [14] and Karnieli et al. [15] separately sought to generate stable insulin-producing cell lines by transducing BMSC with the pancreatic duodenal homeobox 1 (Pdx1) gene. The Pdx1-transduced BMSC expressed several islet-specific genes, produced and released insulin in a glucose-regulated manner, and, when transplanted into streptozotocin-induced diabetic mice, reduced blood glucose levels.
Adipose tissue–derived stem cells (ADSC) are isolated from the stromal vascular fraction (SVF) of adipose tissue and bear a strong resemblance to BMSC [16–18]. Unlike BMSC, however, ADSC can be obtained in large quantities at low risks [19,20]. In addition to being more abundant and easily accessible, the adipose tissue yields far more stem cells than bone marrow on a per gram basis (5,000 vs. 100–1,000) [19]. Therefore, it is reasonable to expect that ADSC may become the preferred choice of ASC for future clinical applications. In regard to their potential as a surrogate β-cell source, two recent articles [21,22] have shown that through the manipulation of the culture media, ADSC could become C-peptide-positive cells, suggesting the potential of ADSC as a surrogate β-cell source. However, these two studies did not describe whether the induced ADSC secreted insulin or whether they were responsive to glucose challenge. Furthermore, similar to the situations with BMSC [10–13], the transient nature of induction makes this approach not clinically applicable. As such, the present study sought to generate stable insulin-producing cells by transducing ADSC with Pdx1 gene. Using both human and rat ADSC, we show that the Pdx1-transduced cells secreted insulin were responsive to glucose challenge, and were capable of reducing glucose levels in STZ-induced diabetic rats.
Source and See More: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862049/