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Summaries of Symposium Speakers' Research

Speaking at the Craig A. Lipkin, MD, Resident Research Symposium at Cedars-Sinai were Michael Choi, MD, Heidi Reich, MD, and Ryan Spurrier, MD. The symposium, part of the Surgery Grand Rounds series, took place May 28 in ECC B-C.

Here are summaries of the residents' current and recent research.

Choi: BRCA Mutations and FOXC1

Michael Choi, MD, working under the guidance of Farin Amersi, MD, and Allan Silberman, MD, PhD, presented his abstract "Analysis of Factors Affecting Outcome in De-Differentiated and Well-Differentiated Retroperitoneal Liposarcomas" at the 2014 Society of Surgical Oncology Cancer Symposium in March. He also had his abstract "The Clinicopathologic Significance of FOXC1 in BRCA-Mutant Breast Cancer" accepted for presentation at the 2014 American Society of Clinical Oncology annual meeting in May.

Choi is working in the Cedars-Sinai Women's Cancer Program laboratory with Xiaojiang Cui, PhD, investigating the association between BRCA 1 and BRCA 2 gene mutations and the related breast cancer transcription factor FOXC1. His clinical research focuses on the prognostic role of FOXC1 in determining the likelihood of recurrence and survival in patients with hereditary breast cancers. The research ultimately will help guide physicians in their clinical decision-making.

He also is examining the significance of the basal molecular phenotype and breast cancer stem cells in trastuzumab resistance for Her2-positive breast cancers under the direction of Alice Chung, MD, and Cui.

Michael Choi, MD, (second from right) presented his poster titled "Analysis of Factors Affecting Outcome in De-Differentiated and Well-Differentiated Retroperitoneal Liposarcomas" at the 2014 Society of Surgical Oncology Cancer Symposium in Phoenix.

Reich: Stem Cells and the Heart

Heidi J. Reich, MD, working in the lab of Eduardo Marbán, MD, PhD, in the Cedars-Sinai Heart Institute, has been participating in clinical trials using stem cells derived from normal, healthy allogeneic human heart tissue delivered through the coronary arteries in patients with myocardial infarction or advanced heart failure. The paradigm to date uses single dosing, but multiple doses may achieve greater benefit, if there are no immune complications.

Heart disease remains the leading cause of death in the U.S. and worldwide. Despite improvements in care for patients with advanced heart failure, mortality within five years of diagnosis remains at 50 percent. Members of the lab are increasingly optimistic that stem-cell therapy will dramatically change this dismal picture by affording a treatment option that can potentially reverse, and maybe one day cure, advanced heart disease.

Reich is studying the immune response to repeat dosing of allogeneic cardiac stem cells. Whether stem cells are immunologically inert or could lead to sensitization has important clinical implications: Rejection or sensitization could reduce the benefit of allogeneic stem-cell therapy, lead to myocarditis or limit future consideration for heart transplantation. Conversely, stem cells that evade the immune system completely can be tumorigenic.

Previous studies in the Marbán lab were encouraging: No detrimental immune response was apparent after single-dose allogeneic cardiac stem-cell therapy. To better characterize the immune response and ensure patient safety, lab members are taking a closer look by giving repeat doses of allogeneic cardiac stem cells and measuring the humoral and cellular immune response in a rat model of myocardial infarction.

Repeat dosing has been found to significantly improve left ventricular ejection fraction on transthoracic echo, and the lab's characterization of the immune response is ongoing.

Spurrier: Engineering Tissue to Treat Gastrointestinal and Liver Failure

Ryan G. Spurrier, MD, completed his postdoctoral research fellowship at Children's Hospital Los Angeles in the Department of Developmental Biology and Regenerative Medicine under the mentorship of Tracy Grikscheit, MD. Spurrier's research focuses on treating gastrointestinal and liver failure through tissue engineering, in which healthy tissues are regenerated from a patient's own stem cells for replacement of a defective or absent organ by auto-transplantation. To further investigate the mechanism of this regeneration, he has worked extensively with transgenic mouse strains and fluorescent cell labeling to study the interactions between mesenchymal and epithelial cells that comprise the intestinal stem cell niche.

Spurrier also has adapted the technique of vitrification to the field of gastrointestinal tissue engineering. Vitrification is a phenomenon wherein supercooled liquid is able to transition almost instantaneously into a solid, glasslike state, allowing for the long-term preservation of living cells. Spurrier demonstrated that vitrified cells can be reanimated and then used to create tissue-engineered small intestine. This cell preservation strategy could expand the reach of tissue-engineered therapies to patients who are too ill to undergo auto-transplantation at the time of tissue resection or who require transfer to a medical center capable of such interventions.

Spurrier also has been active in clinical and basic/translational research regarding cholestatic liver failure, which often affects children with short bowel syndrome requiring total parenteral nutrition (TPN). In collaboration with pediatric gastroenterologist Russell Merritt, MD, he helped carry out the second-largest clinical trial of fish-oil-based TPN in the U.S.

This pilot study demonstrated impressive results, with reversal of cholestasis in more than 90 percent of patients. In the laboratory, Spurrier collaborated with Kasper Wang, MD, to generate the first reported instance of tissue-engineered liver from human stem cells. Furthermore, he applied his vitrification technique to cryopreserve human liver progenitor cells and subsequently thaw these to generate tissue-engineered liver.

Most recently, Spurrier generated human tissue-engineered esophagus. While other researchers have described seeding of tubularized polymers with epithelium alone, growth of full-thickness human tissue-engineered esophagus had not been demonstrated. However, by isolating stem cells from fresh esophagectomy specimens and implanting them into immune-deficient murine hosts, Spurrier was able to regenerate full-thickness esophageal epithelium with supporting muscularis and nerve.

Furthermore, these multicellular isolates were able to proliferate in vitro, where they organized to form a neuromuscular network that enveloped the esophageal epithelium and demonstrated peristaltic contraction, which highlights the functional potential of tissue-engineered gastrointestinal tissues.

Spurrier has presented his research at the Clinical Congress of the American College of Surgeons, the Academic Surgical Congress, Digestive Disease Week, the Southern California chapter of the American College of Surgeons and the Federation of American Societies for Experimental Biology. He also has published in the Journal of Pediatric Surgery and the Journal of Clinical Gastroenterology and Hepatology.

His other ongoing projects include characterizing the microbiome of tissue-engineered intestine and human subjects. He is completing his General Surgery residency at Cedars-Sinai and plans to pursue fellowship training in Pediatric Surgery.