New Faculty II
$2 403 369
This proposed research project will develop a new technique using lasers to identify and characterize stem cells. The identification and characterization of stem cells is an essential first step in the design of effective treatments; however, current techniques for identifying and characterizing stem cells have disadvantages. Since there is no single marker to identify stem cells, a combination of different measurements is currently used to identify them, including cell surface markers, gene patterns, and the potential for differentiation toward certain cell types. Some stem cells can be identified using a specific surface marker, while others do not have unique markers and must be identified based on a combination of surface markers. The most common technique currently used to identify and isolate stem cells is flow cytometry, which requires a large number of cells in suspension and antibodies binding to cell proteins for analysis. These binding techniques have been shown to affect cell function. Raman spectroscopy is a new technique that uses a laser beam to analyze the internal structure of a cell. It can be used to measure the amounts of various biological components in the cell as well as certain molecular characteristics. Unlike flow cytometry, Raman spectroscopy only requires a few cells, does not require cells in suspension, and does not require staining of the cells. Preliminary research indicates that characteristics of human blood cells and embryonic stem cells can be identified using Raman spectroscopy. An important goal of this project is to determine whether this novel application of Raman spectroscopy can be used to identify and characterize stem cells. Among the most promising potential uses of human stem cells are cell replacement therapies and tissue regeneration for diseases. The transplantation of stem cells for the production of new blood cells has been a cure for many serious conditions, including malignancies, genetic disorders, and immune disorders. However, there are limitations with current sources of these stem cells, such as bone marrow and umbilical cord blood. The full-term placenta may be a promising alternative source of stem cells, because it is easy to obtain and not ethically problematic. In addition, stem cells from the placenta have the potential to differentiate into many different cell types. Therefore, placenta-derived stem cells may be very useful for the development of promising new stem cell replacement therapies to treat various diseases. In the proposed project, we will define the Raman spectroscopy “fingerprints” of placenta-derived stem cells and will compare them with the fingerprints of other adult and embryonic stem cells. The project will provide unique methods to investigate and isolate stem cells from different sources and may lead to new uses for stem cells in clinical therapies.
Statement of Benefit to California:
The proposed research project seeks to develop a new technique for identifying and characterizing stem cells from different sources. If successful, this technique will help other stem cell researchers and could lead to new uses of stem cells to treat various pediatric diseases including cardiomyopathies, diabetes, bony disorders, biliary atresia and choledochal cyst (cirrhotic livers), spina bifida, cerebral palsy and muscular dystrophy, in addition to stem cell transplantation for leukemia, sickle cell anemia, and other hematopoietic disorders. This project will directly benefit California and its citizens in several important ways. First, the project will be undertaken at a major California public research institution and will take advantage of the resources of a California-based site of a national network of centers designed to speed up the process of developing treatments for patients from research discoveries. In addition, collaboration with other California-based researchers in this project will increase the benefits of the grant by providing opportunities for the exchange of ideas within the California stem cell research community. Finally, the funding of this project through a CIRM grant will allow the researcher, together with other California researchers and doctors, to investigate a technique that has the potential to dramatically improve the health of many people in California.
The primary focus of this proposal is the characterization of placenta-derived stem cells (PDSC) by Raman spectroscopy. The Raman spectroscopy fingerprint of the PDSCs will be compared with that of stem cells from other adult and embryonic sources. The engraftment and tissue repair potential of the defined PDSC and other stem cells will be investigated in an in vivo model. It was recognized by the reviewers that there may be some advantages of the Raman characterization approach over flow cytometry, such as no requirement for antibody labeling, ability to be used on adherent cells, and only small numbers of starting cells are needed. It was also recognized that PDSC are potentially a novel and useful alternative source of stem cells. However, the reviewers were not convinced that Raman spectroscopy would be able to identify a unique fingerprint of “stemness”. Moreover, it is not clear how this methodology will allow sorting of specific stem cell populations needed for in vivo characterization and comparison with other stem cells, as this is not clearly described and the methodology does not appear to have this capacity. In addition, the preliminary data are not particularly compelling. More importantly, the preliminary data are not explained in a way that allows understanding of the statistical methodology. In the proposal, the principal investigator (PI) claims that the Raman Spectroscopy approach will be useful for therapeutic isolation of stem cells, but no details are provide on how this might be achieved. It does not appear that the technology would scale easily to be able to handle the larger cell numbers needed for in vivo research or later therapeutic applications. The PI has a hematology/oncology background. His/her publication record is limited having focused on chromosomal abnormalities in leukemia. The PI’s institution has a strong stem cell environment. The structure of the mentoring program for the PI is not very clear. There are no letters from scientists or collaborators that support and mentor the applicant. Because of these reasons enthusiasm for this proposal was muted.