HUMAN EMBRYONIC STEM CELLS

Human embryonic stem cells (hESCs) are nature’s master stem cells. They are a self‑renewing source for the scalable manufacturing of functional replacement cells for every tissue and organ in the body. The hESCs with which Geron works were derived from surplus in vitro fertilized embryos originally created as part of an in vitro fertilization (IVF) procedure. The embryos, which would otherwise have been destroyed, were donated for research by the parental donors under informed consent. The hESC line that is used to produce GRNOPC1 is the H1 line. Studies using this line qualify for U.S. federal research funding, although no federal funding was received for the development of the product or to support the clinical trial.

hESCs have two characteristics that make them different from other naturally occurring stem cells. First, they are immortal – they express the enzyme telomerase that enables the cells to divide endlessly in tissue culture. This allows scalable manufacturing of therapeutic cells derived from a master cell bank. Second, hESCs have the ability to differentiate into any of the more than 200 functional, specialized cells that make up the tissues and organs of the human body. Geron scientists have learned how to grow undifferentiated hESCs under carefully defined conditions, enabling them to be numerically expanded to form large cell banks (hundreds of vials of frozen undifferentiated hESCs) that serve as uniform starting material for manufacturing procedures that convert the undifferentiated hESCs into functional therapeutic cells. Geron scientists have learned how to manufacture seven different types of functional cells from hESCs:

• neural cells to treat chronic degenerative diseases of the nervous system;
• cardiomyocytes for the treatment of congestive heart failure and myocardial infarction;
• islets for the treatment of diabetes;
• chondrocytes for the treatment of osteoarthritis;
• hepatocytes for ADME drug testing;
• dendritic cells cells for immunotherapy for cancer and infectious diseases; and
• osteoblasts for the treatment of osteoporosis and bone fractures.

These functional cells are produced from hESCs by specific processes in which the frozen, banked hESCs are thawed, numerically expanded in their undifferentiated state and then treated with specific biologicals and growth factors to induce them to differentiate into specific functional cell types for therapeutic use. Each cell type requires a unique manufacturing “recipe.” All of the differentiated cells produced by the manufacturing process are normal, healthy cells that have not been genetically modified and which have characteristics similar to the equivalent “natural” cell type present in the body.