Isolation, purification, cryopreservation, expansion, differentiation and characterization of homogeneous populations of cells derived from the placenta and amnion for therapeutic use.
Embryonic stem cells (ESC) are able to be grown indefinitely and be differentiated into all types of tissues such as blood, bone, brain, bone, liver, etc. Unfortunately, a number of bottlenecks in regard to the use of these cells in clinical trials exist. These include the possibility that these tissues may give rise to tumors, the need to grow these cells in ways that might introduce contaminants, many social and ethical issues, technical challenges to growing large numbers of cells, and the difficulties associated with initiating clinical trials using these cells . Adult stem cells found in cord blood and bone marrow are currently used in clinical trails and have demonstrated efficacy. Stem cells (SC) collected from the umbilical cord at the time of birth (called cord blood) have been shown to be an important resource for transplantation for malignant and genetic conditions. These cells have a number of advantages over hematopoietic stem cells collected from the bone marrow later in life, including greater proliferative potential, greater potential to differentiate into diverse types of cells, reduced presence of infectious agents such as CMV, and less exposure to environmental mutagens. However, cell number, costs, logistics of collection, and limited banking of collected units due to the limited number of stem cells per unit of cord blood and limited pluripotency represent bottlenecks to cord blood derived. Furthermore, there are differences in certain characteristics of cord blood units collected from African Americans that limit the number of cord blood units appropriate for African Americans. This has a serious detrimental impact on the care of African American patients who need a stem cell transplantation. Another type of stem cells -- induced pluripotent stem (iPS) cells -- constitute an exciting new area or research believed to generate cells similar to ESCs. The current technology involved in generating these cells however, poses other concerns about causing tumors if such cells were to be transplanted into humans. Thus, there remains a need to identify a source of pluripotent stem cells that can be used for clinical trials in the near term. We believe that our proposal which will use stem cells derived from the human placenta or a membrane surrounding the placenta, called the amnion, will generate such a source of pluripotent stem cells. The availability and quantity (over 600,000 births/year in California, 4 million/year in the United States and over 250,000/year in Australia) of placenta and amnionic membranes and the easy non-invasive access and minimal ethical, legal, moral issues associated with their collection and usage, makes these gestational, fetal-like tissues an attractive source of pluripotent stem cells. But first, it is necessary to prove that pluripotent stem cells can be derived from the placenta and amnion and that they are not subject to the limitations associated with embryonic stem cell sources.
The proposed research holds the promise of providing a new source of pluripotent stem cells that potentially could become any type of tissue. The overall objective of our collaboration is to develop procedures whereby pluripotent stem cells found in the placenta and its amnionic membrane can be readily obtained, isolated, stored, and characterized so that they can be used safely in near term clinical trials to evaluate their efficacy in treating human diseases. Our hypothesis is that these stem cells will overcome many of the bottlenecks limiting near-term therapeutic applications associated with other sources of stem cells, particularly embryonic.