Pancreas & Liver Program

Faculty

Vaithi Arumugaswami, MVSc, PhD
Donald Dafoe, MD


Mission

The mission of the Pancreas and Liver Program at Cedars-Sinai Regenerative Medicine Institute is

  • to develop stem cell-based regeneration approaches for the treatment of hepatitis C and alcoholic liver disorders
  • to develop treatments for diabetes mellitus that will also benefit patients with other types of diabetes

Focus of Pancreas Research

The focus of our pancreas research is to use induced pluripotent stem cells (iPSCs) to derive mature insulin-producing beta cells that can respond to glucose challenges in culture. Our ultimate goal is to transplant the mature beta cells into patients with type I diabetes mellitus to properly regulate their glucose levels.

The iPSC technology allows for the study of differentiation and maturation of pancreatic beta cells in a microenvironment similar to that found in the body. We have developed a complex cell culture microenvironment enriched with endothelial cells and vascular basement member components (named collagen IV and laminin) in which human iPSCs differentiate into pancreatic beta cells.

We were the first to obtain a large number (up to 90 percent) of stem cell-differentiated pancreatic beta cells in culture. These cells expressed many key markers of mature beta cells. Our preclinical experiments indicate that these cells respond to glucose after transplantation in animals, and they do not develop tumors.

Insulin-producing beta cells (red and green colored) derived from human stem cells.



Focus of Liver Research

The liver is the second most commonly transplanted organ in the United States. However, there are an estimated 16,500 people awaiting a liver transplant at any given time and only 3,000 available organs. Most liver damage is due to the hepatitis C virus (HCV).

Our research focus is on rejuvenating the damaged liver without requiring transplantation. This approach could provide the medical community an additional treatment option for managing patients with disorders of the liver, including HCV.

Regenerative Medicine liver researchers can generate functional liver cells from pluripotent stem cells, including iPSCs. The human stem cell-derived hepatic cells have been shown to extend the survival of mice with liver damage and do not produce any adverse events, including teratoma formation. This cell therapy is translatable to clinics as an individualized patient-specific treatment.

Our research is also focusing on engineering an artificial liver using natural or synthetic scaffold materials.

 

Generation of natural scaffold for engineering whole liver organ in a dish.



Collaborative Research

The Regenerative Medicine Pancreas and Liver Program is collaborating with other Cedars-Sinai departments and institutes including the Department of Surgery, Comprehensive Transplant Center, and Diabetes and Obesity Research Institute on artificial organ devises and diabetes model systems.

Through an interdisciplinary collaboration, liver research investigators have also developed a robust methodology to improve gene engineering in stem cells, which provides the option of generating disease-specific therapeutic stem cell lines.

Finally, liver research investigators are partnering with industry to assess leading-edge technology using scaffolding to generate artificial livers.