BME Seminar Series: Dr. Shreya Raghavan, University of Michigan
"Engineering the stem cell microenvironment in regenerative medicine and cancer"
Tissue microenvironments are diverse in cellular, architectural, mechanical, and material cues and play an important role in stem cell differentiation – be it during tissue regeneration or in cancer.
An example of microenvironment engineering for tissue regeneration is the use of biomaterials-based hydrogels to direct the differentiation of neural stem cells to specific motor neuronal subtypes. When differentiated motor neurons are integrated with engineered gastrointestinal smooth muscle, they regulate motor function, creating functional innervated intestinal tissues. These engineered tissues can in turn be used in transplantation settings to remedy gastrointestinal motor pathologies (like those arising from diabetes).
In cancer, microenvironment engineering can be utilized to create 3D in vitro tumor models for drug screening, and to study cancer biology. An example of engineering the stem cell environment in cancer includes creating a non-adherent hanging drop array system, where 3D spheroids can be generated from primary patient-derived ovarian cancer stem cells. In suspension culture, cancer stem cells differentiate to mirror primary tumors, and can faithfully mimic patient response to platinum chemotherapy in vitro.
Tissue-resident adult stem cells have the potent ability to regenerate given the right cues, to repair and restore organ function. Similarly, stem cells can also remain quiescent, and repopulate a tumor, when under attack from chemotherapy. Engineering stem cell niches can answer broad ranging questions from cancer recurrence and escape from chemotherapy to functional tissue engineering and regeneration.
Dr. Raghavan is a biomedical engineer, with a strong interest in using tissue engineering and regenerative medicine principles to study stem cell/immune interactions. Her doctoral training involved the use of a variety of biomaterial microenvironments to direct the differentiation of enteric neural stem cells. These differentiated nerves were then used to create functional neural networks within bioengineered intestines, for transplantation. During her postdoctoral tenure, she shifted her focus to using tissue engineering strategies to build micro-tissue models of ovarian cancer from patient-derived cancer stem cells. The goal of her study was to understand ovarian cancer progression and chemoresistance from a stem cell point of view. Dr. Raghavan is the recipient of the Ruth L. Kirschstein National Research Service Award from the NIH, to aid in her postdoctoral training in tissue engineering. She serves as a mentor in the Undergraduate Research Opportunities Program, and the Women in Science and Engineering program at Michigan, and is committed to teaching, and scientific service. She also serves on the Dean’s Advisory Council for the Michigan Postdoctoral Association, where she advocates for postdoc equity and inclusion in the academy.