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BE Seminar – Ariella Shikanov, “Bridging Engineering and Biology: New Frontiers in Ovarian Function Restoration and Fertility Research”
January 29 at 3:30 PM - 4:30 PM
Premature ovarian insufficiency (POI) and infertility are irreversible and life-altering consequences of radiation and chemotherapy, significantly affecting young cancer survivors. Restoring reproductive function in women poses a unique challenge, as they are born with a finite and non-renewable reserve of ovarian follicles—the ovary’s functional units, each containing a single oocyte and hormone-producing somatic cells. Current clinical options for restoring lost ovarian endocrine function are limited to hormone replacement therapy (HRT), which provides only a subset of gonadal hormones in a continuous fashion, unlike the cyclical and pulsatile hormone patterns found in healthy young women.
To address these limitations, my lab has developed a cell-based therapy that delivers the full spectrum of ovarian hormones at physiological levels and rates, and is capable of responding to feedback from the body. This innovative therapy uses an immune-isolating hydrogel capsule with a degradable core and a non-degradable shell to encapsulate and implant donor ovarian tissue. The design enables growth and expansion of the ovarian grafts while effectively preventing immune cell infiltration. In studies with immunocompromised and immunocompetent ovariectomized mice, implantation of encapsulated human ovarian tissue successfully restored estrous cycles and produced systemic estradiol levels, correlated with the presence of large antral follicles in the grafts—results comparable to non-encapsulated controls.
Our research also aims to enhance in vitro ovarian follicle development. We have engineered biomimetic matrices that support the deposition and retention of extracellular matrix (ECM) molecules secreted by cultured follicles and cells, replicating the fibrous structure of native ECM to better support folliculogenesis.
Lastly, the engineering efforts in my lab are closely integrated with biological discovery. Recently, we published a high-resolution spatial cell atlas of the human ovary and sequenced individual oocytes from human primordial follicles by combining spatial transcriptomics with single-cell RNA sequencing. By profiling over 18,000 genes in carefully selected ovarian regions, we revealed localized gene expression patterns and distinct cellular architectures. This spatially resolved atlas, highlighting new molecular markers and structure–function relationships critical to fertility, hormone production, and ovarian aging, serves as a valuable resource to optimize biomimetic platforms for follicle growth both in vitro and in vivo. Ultimately, our research aims to advance cures for infertility and loss of ovarian function through innovative therapeutic approaches.
Ariella Shikanov, PhD
Professor, Department of Biomedical Engineering, University of Michigan
Dr. Shikanov is a Professor in the Department of Biomedical Engineering at the University of Michigan. She currently serves as the Associate Director of the Cellular and Molecular Biology Graduate program at the Medical School and served as an Associate Chair of Undergraduate Engineering for 5 years. Dr. Shikanov earned a Ph.D. in Medicinal Chemistry and Pharmaceutical Sciences, followed with postdoctoral training in the Department of Chemical and Biological Engineering at Northwestern University with Drs. Lonnie Shea and Dr. Teresa Woodruff, pioneers in reproductive tissue engineering. Since starting her lab at the University of Michigan in 2012, she has established a research program focused on ovarian function, fertility preservation, and reproductive health.
A major focus of her work is restoration of ovarian endocrine function and fertility utilizing biomimetic and microporous annealed particle hydrogels to promote human ovarian graft revascularization and immuno-isolating capsules for donor ovarian tissue transplantation.
Dr. Shikanov’s lab is also developing biomimetic matrices to promote folliculogenesis in vitro, and investigating the reproductive consequences of testosterone administration in transgender individuals. Her research is highly interdisciplinary, integrating biomaterials, reproductive biology, and regenerative medicine to address urgent clinical needs in women’s health.
Her contributions have been widely recognized, with support from multiple NIH R01 grants, the Chan Zuckerberg Initiative, an NSF CAREER Award, and the Cellular and Molecular Bioengineering (CMBE) Young Innovator Award. She is also a Fellow of the American Institute of Medical and Biological Engineering (AIMBE), reflecting her leadership and impact in the field.