PFDD Faculty Fellows Alumni - 2009

2009 HARVARD CATALYST

PROGRAM FOR FACULTY DEVELOPMENT AND DIVERSITY INCLUSION (PFDD)

FACULTY FELLOWSHIP - BCH

Carlos R. Estrada, MD, Associate Professor of Surgery (Urology), Harvard Medical School; Associate in Urology, Department of Urology, Boston Children’s Hospital, Director, Spinda Bifida Center; Director, Voiding Improvement Program


Mentor: Michael R. Freeman, PhD, Program Director, Children’s Hospital/Harvard Urological Diseases Research Center, Professor of Surgery, Harvard Medical School

Department Chair: Alan B. Retik, MD, Urologist-in-Chief, Children’s Hospital Boston; Professor of Surgery, Harvard Medical School

Project Summary: Novel Bladder Tissue Engineering: Induced Pluripotent Stem Cell-Derived Smooth Muscle Cells and Uroepithelial Cells and Silk Biomaterial Scaffolds

Abstract:

The optimal scaffold material and patient-specific cell source for tissue engineering (TE) of the urinary bladder remain elusive. Uniting the resources of the Harvard Stem Cell Institute and the Urological Diseases Research Center at Children’s Hospital, I will interrogate the use of silk-based biomaterials in combination with induced pluripotent stem cell (iPS)-derived bladder cells to address this need. Silk-based biomaterials provide an exceptional combination of physical properties that are well suited to bladder function, and are readily modifiable to optimize these properties as well as cellular seeding, proliferation, and in-growth of surrounding tissue.

Recently, our collaborators published the first description of induced pluripotency in fibroblasts derived from an adult human skin biopsy. These cells were reprogrammed to pluripotency by the ectopic expression of four transcription factors, and the resultant induced pluripotent stem (iPS) cells closely resembled embryonic stem (ES) cells. Using methods we have developed using ES cells, we will derive smooth muscle cells and uroepithelial cells from iPS cells. These cells will be combined with silk-based biomaterials that are engineered to mimic the extracellular matrix of the bladder. The novel constructs will then be utilized for murine bladder augmentation to test the functional capacity of the constructs and interrogate the phenotypic stability of the iPS-derived cells. This project may ultimately inform pre-clinical trials testing similar constructs in patients who require bladder augmentation to treat end-stage bladder decompensation and its complications.

Biography:

Carlos Estrada is a former Instructor in Surgery (Urology) and an Assistant in Urology at Children’s Hospital, Boston. His research project is entitled Novel Bladder Tissue Engineering: Induced Pluripotent Stem Cell-Derived Smooth Muscle Cells and Uroepithelial Cells and Silk Biomaterial Scaffolds.