New Faculty II
$1 623 646
Human stem cells hold great potential for use in stem cell-based therapies and regenerative medicine. Technologies developed to date, however, cannot create patient-specific embryonic cell lines; hence transplanting these cells poses innumerable immunological barriers. Another obstacle for embryonic stem cell use is their propensity to form tumors. Human placenta is a potential source of primitive fetal stem cells, yet it is poorly studied. Large volumes of placental tissue could provide abundant numbers of primary stem cells which will eliminate lengthy ex vivo stem cell propagation. My hypothesis is that the tissue of human term placenta is a high capacity source of embryonic-like stem cells capable of differentiating into all tissue types in the human body. In this project, I will demonstrate the potential of cells of human term placenta to differentiate into different tissues. I will obtain cells from placenta tissue digests and isolate cells expressing surface markers of human embryonic stem cells. Cells will be characterized by their morphology, ability to propagate long-term in culture, expression of human embryonic cell-specific markers, and formation of tumors in mice. Analysis of gene structure will be performed in late passages. I will test the potential of embryonic-like cells to facilitate repair of injured epithelium. Use of placental stem cells will greatly reduce the need for embryonic stem cells, which, to date, cannot be obtained without destroying human pre-implantation embryos. Placenta as a source of abundant numbers of stem cells will greatly lessen the need for stem cell line propagation. Cryopreservation of individual placentas would provide a life-long source of personal stem cells. If the aims of the application are achieved, novel therapies will likely result.
Statement of Benefit to California:
Stem cell-based therapies are the promising future of medicine. The application of this treatment is limited because of the restricted supply of appropriate stem cell lines, as it is necessary to match certain characteristics of the donor’s and host’s immune systems. I have carried out pioneering studies demonstrating that human placenta may be used as a source of such stem cell lines. These cell lines derived from human placenta will contribute to research in stem cell biology and clinical applications. Furthermore, placentas are readily available from any individual giving birth. As this approach does not require the donation or use of either human embryos or eggs, it will greatly reduce the ethical concerns, and may help overcome the limitations inherent in obtaining excess human embryos. As such, I will be able to generate stem cell lines that will reflect the diverse population of California. Diseases that can potentially be cured by the use of stem cell treatment afflict a significant number of individuals in California. These stem cell lines will be used in regenerative medicine research and cell replacement therapies as well as the development of new treatment approaches. The enhanced and extended lives of the individuals will represent an evident benefit; the savings to the health care system as a consequence of their cure will straightforwardly benefit all California taxpayers. Ultimately the knowledge and experience produced by the work proposed will contribute to the goal of making stem cell transplantation and new medical approaches available to a much broader group of patients, thus greatly extending the benefits to the affected individuals and to the taxpayers of California. Storage of human placentas as a source of patient-specific stem cells through the life of each individual will some day become a medical necessity, and California may become the pioneer in this breakthrough initiative.
The investigator proposes to test the hypothesis that the human placenta will provide a source of two types of stem cells, mesenchymal and embryonic-like, that will have therapeutic value. These cells will be purified, tested for pluripotency and then examined in detail for the ability to differentiate into different cell types including cells suitable for the repair of lung injury. The potential of the differentiated cells for repair will be evaluated in both ex vivo and in vivo models of lung injury. Isolating stem cells from the human placenta is an emerging field of research that holds potential as a source of new lines/types of stem cells. However, the reviewers found the experimental description to be highly superficial with respect to cell isolation, culture and placenta biology, and therefore could not confidently judge the project to be feasible. Insufficient detail was provided in the research plan about the characterization of the embryonic-like stem cells, and therefore reviewers were unclear as to what these proposed cells actually are. With respect to the final aim, reviewers expressed confidence that the applicant could execute the ex-vivo testing, noting previous experience with that model. However, insufficient detail was provided about the in vivo lung injury model for reviewers to evaluate the feasibility of this part of the proposal. The applicant is a pulmonary physiologist with experience working with both bone marrow stem cells and working with placental tissue. She/he listed 17 publications, but very few are in mainstream journals. Currently the applicant has no external funding. The mentoring plan is adequate. The applicant has been on the faculty at the institution since 2004, is a professor at another institution outside of California, and has a senior position at yet another institution also outside of California. The reviewers presumed that the applicant would need to devote some time towards these other appointments and expressed concern about how much time she/he will be able to spend on this proposal. This was of concern to a reviewer since the applicant is in the very early stages of establishing a career as an independent investigator in stem cell research. Another reviewer questioned the appropriateness of the applicant for this award given the senior level of his/her other positions. There is a strong letter of support from the head of the institution that includes a clear indication that the applicant will be completely protected from clinical responsibilities. The institutional environment appears sufficient for the applicant to accomplish his/her scientific goals.