The present invention relates to methods comprising of specialized mononuclear cells from bone marrow that can rescue hyperglycemia and augment pancreatic repair.

BACKGROUND: Diabetes affects over 18M Americans with almost 90% of these being attributed to environmental factors and lifestyle decisions.  In the US and Europe alone, the number of type II diabetes patients is expected to rise to ~41.5M by 2012.  In contrast to type I diabetes, in type II diabetes the individual genetics of pancreas function are intact and pancreatic dysfunction is related to the very slow rate of regeneration of the pancreas following damage.  The ultimate goal of next-generation technologies is to replace the current exogeneous insulin delivery treatment of diabetics with a regenerative strategy.

 

The traditional hope for stem cell biology is that autologous or modified allogenic stem cells will someday be delivered to diseased individuals to regenerate functional insulin producing islet cells and ultimately repair diseased organs.  This dream is becoming less realistic as one considers the technical requirements to implement this strategy including limiting the cancer-initiating potential of stem cells, instructing stem cells what cell type to become and how, and adequately delivering and directing cells to the appropriate site of engraftment.  As such, there is currently no accepted progenitor cell therapy for the treatment of diabetes in humans. In contrast, therapeutic strategies that can augment the limited natural regenerative properties of insulin producing pancreatic cells are becoming fashionable in combination with, or replacement of, stem or progenitor cell therapy. 

 

DESCRIPTION OF THE INVENTION: The present invention relates to methods comprising of specialized mononuclear cells from bone marrow that can rescue hyperglycemia and augment pancreatic repair. The cells are distinguishable from classic circulating hematopoietic stem cells and stimulate the repair or regeneration of endogenous islet cells. They can be isolated directly from bone marrow and applied without culture in vitro. The cells do not themselves transform into islets but instead stimulate endogenous cells to re-enter the cell cycle and generate insulin producing cells. This inductive property of the transplanted cells is specific to damaged tissue and the cells do not incorporate under healthy conditions. The system has been demonstrated to be valid in mouse models and may serve an equivalent therapeutic function in humans.

 

POTENTIAL ADVANTAGES/USES:

• Promoting endogenous repair will allow the body to naturally control its insulin levels without using exogenous insulin delivery
• Harvest and transplantation can be autologous and thereby limiting concerns of immune response
• Direct application of harvested cells limits change in stem cell properties with culture in vitro
• Marrow derived cells are capable of rescuing hyperglycemia and reduce blood glucose levels in a diabetic mouse model
• Cells home to the site of damage and do not have to be administered locally.
• Cells may serve as a model system to explore new targets of endogenous islet cell induction

 

Keywords: Pancreatitis, Diabetes, Islet cells, Regeneration initiating cells, Stem cells, Cell-based therapy, Regenerative medicine, Bone marrow, Insulin, Hyperglycemia, Mouse model, Target discovery, Cell surface marker

Preclinical

National Phase protection.