The structure that we have built in the last decade serves as the basis for this new proposal, although it is now both expanded and redirected. The Center for Cell Therapy (CTC) initially brought together a group of researchers in cell and molecular biology, genetics, protein chemistry, bioinformatics, and hematology who developed collaboration and synergism in research, and a strong capacity to develop a program in a field that was new at the time, linking it to the well-established cancer research, especially blood malignancies. This association had a strong positive effect on the scientific output. We defined many characteristics of the mesenchymal SC (gene expression profile, widespread occurrence, relationship with pericytes and fibroblasts, molecular mechanisms underlying their immunomodulatory role). We revealed the role of the NF kappa B pathway in primitive progenitors, and a wealth of molecular mechanisms in blood neoplastic cells (expression of CT-antigens, miRNA expression profile, and the role of TGF-beta, MDR1, and telomerase). We were the first Brazilian group to establish new human embryonic SC lines and to publish on iPS cells. On the clinical setting, we demonstrated that high-dose chemotherapy followed by autologous hematopoietic SC transplantation is a feasible way to treat type 1 diabetes mellitus.
The incorporation of experts in telomere biology, in large mammal ooplasmic transfer and cloning, and in embryonic and iPS cells allowed the expansion and redirection of our research. The present proposal is to develop basic and clinical research to isolate, expand, and characterize embryonic, pluripotent, somatic, and neoplastic stem cells (SC) in order to understand their biology and apply this knowledge to therapy, comprising four research lines: (1) pluripotent SC (embryonic SC and induced pluripotent SC); (2) somatic SC (hematopoietic SC, mesenchymal SC, endothelial SC, and cancer SC); (3) general mechanisms involved in maintaining “stemness” (epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions); and (4) clinical SC applications.
One of the reasons for the success of the Center is that it was entirely located in ample and well-equipped facilities on the University of São Paulo (USP) campus in Ribeirão Preto. It is not a “virtual” network, but a real research institute that allows permanent interaction between senior and younger researchers and interdisciplinary collaboration. Most laboratories and facilities are located at the Ribeirão Preto Blood Center, in addition to laboratories, wards, and outpatient clinics at the University Hospital at walking distance from the Blood Center, where experts work on hematology, immunology, protein chemistry, genetics, cell and molecular biology, virology, and bioinformatics. This is complemented by supporting facilities for animal care, teaching, the science education program, and management support (clerical, documentation, procurement, and accounting).
This new proposal includes two additional laboratories off campus. One is located at the School of Animal Sciences and Food Engineering, at the USP campus in Pirassununga (100 km away from Ribeirão Preto), where scientists working on ooplasmic transfer and mammal cloning are based on. In the other laboratory, scientists are experts on embryonic stem (ES) cell derivation and ES and iPS cell biology, and it is located at the Institute of Biology, at the USP campus in the city of São Paulo (300 km away from Ribeirão Preto). These three groups have interacted in the last five years and constitute the National Institute for Stem Cell Research and Cell Therapy sponsored by the Ministry of Science and Technology since 2008.
The other strength of our Center is the capacity to train human resources. Since the creation of the Center, we have qualified 60 MSc and 68 PhD students and 31 postdoctoral fellows. To strengthen this effort, we have organized a new graduate program (with two tracks, one academic and another professional) that will begin to enroll the first candidates in the fall of 2012.
We propose a three-fold approach for technology transfer: (a) cooperation with the private sector (new therapies, recombinant proteins, and diagnostic methods); (b) cooperation with the government; and (c) education of a new generation of scientists and high level technicians, fostering entrepreneurship, innovation, and generation of spin-off companies. An integral part of the technology transfer is the contribution of the Center for Cell Therapy to the Ribeirão Preto Blood Center by improving and diversifying services offered to the community. It is the only Blood Center accredited and certified by ISO9001 and the American Association of Blood Banks (AABB) in the State of São Paulo, with more than 160,000 registered donors, 8,000 donations/month, and 12,000 clinic visits of patients with blood disorders, and more than 150,000 blood components transfused yearly. The Center has developed a nucleic acid testing for HIV and HCV that is now applied routinely to 10,000 blood donations/month, and this technology has been transferred to the State Department of Health. The Center’s experience led to the establishment of a Cryobiology Laboratory, Umbilical Cord Blood Bank, and a GMP Tissue Culture facility, which allows, for instance, the culture of mesenchymal SC for clinical trials. Within this model, our targets for the immediate future are: (1) the generation of an iPS cell library based on the Brazilian ethnically diverse population, (2) to scale up processes for cell therapy, (3) use of stem cells as biofactories, and (4) the development of molecular diagnostics (telomere length in blood cells for telomere diseases and infections relevant to cell therapy: mycoplasma, CMV, human parvovirus B19, and HTLV).
Thus far, more than 2,000 middle-school students and 150 teachers have participated in the science education program that will now be reinforced, keeping its basic feature of focusing on a long-term relationship between the center and middle-school students and teachers.
The two university institutions involved in the creation of the Center will provide significant counterpart to match FAPESP’s support. USP will provide two new full-time tenure-track faculty positions, three full-time technicians, and one administrative manager to the Center. Innovation and technology transfer is supported by USP Innovation Agency that comprises 35 dedicated personnel including innovation agents and lawyers. USP will continue to provide 1,500 m2 of lab and ward space (paying for basic expenses). The Blood Center (and Hemocentro Foundation, the Blood Center supporting civil organization) will continue to provide 5,200 m2 in laboratory space (paying also for basic expenses, such as utilities without overhead charges) for research and education, clerical, documentation, and management support, paying also for 21 technical personnel actively engaged in research, in addition to paying salaries for six full-time staff scientists, four of them with PhD degree.