Year 5

The Sanford-Burnham Medical Research Institute (SBMRI) Stem Cell Research Center (SCRC) and Core Facility (SCC) supports research that (a) involves a range of pluripotent & somatic stem & progenitor cell types; (b) examines the behavior & therapeutic use of exogenous & endogenous stem/progenitor cells in animal models of a range of diseases & organ systems with an eye towards clinical translation; (c) leverages the unique strengths & resources of SBMRI, including high-throughput screening, & epigenomic, proteomic, microRNA, & metabolomics. In addition, SCRC has become an epicenter for education, data exchange, & collaborations on the Mesa.
As the goal for the SCRC SCC is to be the top stem cell facility in the nation, new technology development has been the major focus besides the service projects. Since generating induced pluripotent stem cell (iPSC) is the major service provided by the SCC, further improvement in the reprogramming technology was carried out, including identifying better reagents and optimal condition for each step, adjusting the protocol for different tissue samples, increasing the sample throughput to reduce the cost, etc. In collaboration with Intrexon, a 96-well format reprogramming method was established using a computer controlled laser system. 8-12 samples can be performed simultaneously on one plate. The throughput was increase 10 folds and its reagent cost is only 1/10 of the previous method. In addition to the successful reprogramming on the Epstein-Barr virus immortalized lymphoblastoids, the SCC successfully reprogrammed the umbilical cord blood cells. This achievement along with the high throughput reprogramming method makes it feasible to establish a library of iPSCs from the healthy individuals with an enormous diversified genetic background. Because of this broad range of normal individuals with different immunocompatability markers (called “human leukocyte antigens” or “HLA types”), it would be easy to locate the cell line that has the closest matching HLA type to the patient. The specialized cells can be derived and are immediately suitable for transplantation into the patient without the need for immunosuppression. This enormous potential in future cell therapeutics has been recognized by many cord blood banks. Partnerships with national and international cord blood banks on iPSC generation from healthy donors are expected to be established in 2014.
. The Characterization Sub-Core profiles hESCs, hiPSCs, & somatic stem cells using of immunocytochemistry &cytometry; gene microarrays & deep sequencing; quantitative PCR, methylation, SNP, & microRNA/SiRNA screens; large-scale comprehensive (phospho)proteomics, metabolomics, & pharmacogenetics; & high-resolution cellular imaging – all with an eye to identifying biomarkers for the diagnosis, prognosis, progression, & therapeutic options for such disorders. Via the SCRC website, the largest comparative phosphoproteomic dataset in any biological system, comparing human pluripotent stem cells with their pure neurectodermal derivatives can accessed publicly. Advanced gene microarrays, quantitative PCR, microRNA screens, & proteomics were used to provide genomic fingerprinting of an array of human stem cell lines & their differentiated progeny.
The SCRC’s successful service program has been facilitating local stem cell related research. Many of these projects produced high quality papers published in the first tier scientific journals. In 2013, the researchers in SCRC published 63 stem cell research papers in the areas of degenerative disease, stem cells & regenerative biology and development & aging.
To further enhance the collaboration among the stem cell labs, SCRC hosts the monthly Southern California Stem Cell Consortium and invites top stem cell researchers to present their exciting new discoveries. A monthly stem cell User’s meeting and a monthly Journal Club organized by the SCC are all designed to engage researchers & trainees throughout the region. Being a training facility, SCRC also provides various hands-on training courses on hESC/hiPSC maintenance, hiPSC generation, lineage-specific differentiation, etc. Newly updated protocols for stem cell differentiation & somatic cell reprogramming have been posted to the SCRC website. SCRC also conducts numerous tours to non-stem cell scientists, non-scientists, patient advocates, journalists, donors, high school students, & residents from the local communities who are interested in learning about stem cell biology.