Therapeutic Differentiation of Tumor-derived Insulin-producing Cells Selected for Resistance to Diabetogenic Drugs

نویسندگان

  • Konstantin Bloch
  • Pnina Vardi
چکیده

Differentiation therapy has been proposed as a new approach to selectively engage the process of tumor cell differentiation during chemotherapy of cancer. Our recent in vitro study suggests that such an approach can be extended and utilized for the selection of tumor-derived insulin-producing cells for transplantation. Repeated treatment with streptozotocin selected toxin resistant subpopulation of insulin producing tumor RINmS cells, characterized by increased level of insulin content and secretion. In the present study RINmS cells were found to have higher glucose sensitivity and insulin response compared with parental RINm cells. In addition, compounds known to induce elevated level of cAMP in beta-cells, such as isobutyl methyl xanthine, and forskolin, potentiated glucose-induced insulin secretion of RINmS, but had no effect on the naive parental RINm cells. These experiments suggest that differentiation therapy can be utilized for engineering insulin producing cells with improved defense and secretory mechanisms.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells into Insulin Producing Cells Using Minimal Differentiation Factors

Background & Aims: Type 1 diabetes, or insulin-dependent diabetes, is an autoimmune disease in which pancreatic beta cells are destroyed by the immune system. Hitherto, no definite treatment has been found for this condition. Mesenchymal stem cells (MSCs) are multipotent, self-renewing cells that have the ability to differentiate into mesodermal tissues. This ability has attracted the attention...

متن کامل

Differentiation Potential of Nestin (+) and Nestin (-) Cells Derived from Human Bone Marrow Mesenchymal Stem Cells into Functional Insulin Producing Cells

The feasibility of isolating and manipulating mesenchymal stem cells (MSCs) from human patients provides hope for curing numerous disease and disorders. Recent phenotypic analysis showed heterogeneity of MSCs. A nestin progenitor cell is a subpopulation within MSCs which plays a role in pancreas regeneration during embryogenesis. This study aimed to separate nestin (+) cells from human bone mar...

متن کامل

Pancreatic Differentiation of Sox 17 Knock-in Mouse Embryonic Stem Cells in Vitro

The way to overcome current limitations in the generation of glucose-responsive insulin-producing cells is selective enrichment of the number of definitive endoderm (DE) progenitor cells. Sox17 is the marker of mesendoderm and definitive endoderm. The aim of the present research was to study the potential of Sox17 knock-in CGR8 mouse embryonic stem (ES) cells to differentiate into insulin produ...

متن کامل

بررسی اثر مهاری سلول‌های بنیادی مزانشیمی بافت چربی بر روی تکثیر سلول‌های تک هسته‌ای طحالی موش دیابتی C57BL/6 در محیط آزمایشگاه

Background: Type 1 diabetes (T1D) is a T-cell mediated autoimmune disorder in which pancreas beta-cell destruction causes insulin deficiency and hyperglycemia. In addition to daily insulin treatment, allogeneic islet transplant inT1D is another therapeutic way that needs immunosuppressive drugs to control autoimmune damage and graft rejection. Since life-long application of these drugs is ...

متن کامل

Differentiation of Mesenchymal Stem Cell toward the Insulin-like Cells with Lentivirus Vector Mir-375

Background & Objective: Type1 diabetes is characterized by autoimmune destruction of pancreatic β cells, leading to reduced insulin secretion. Differentiation of mesenchymal stem cells (MSCs) into β-like cells offers new ways of diabetes treatment. MSCs can be insulated from the human umbilical cord tissue and differentiate into insulin-producing cells. Material & Methods: Human um...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • International journal of experimental diabetes research

دوره 1  شماره 

صفحات  -

تاریخ انتشار 2000