Osteoporosis, urogenital complications and other health risks are common in women who have a loss in ovarian hormones due to menopause or other causes of ovarian failure. Pharmacological hormone replacement therapy (pHRT) has been used for decades in women who have gone through menopause. However, in the past 20 years, pHRT use has decreased significantly due to concern over increased risk of heart disease and certain cancers. A variety of aspects may contribute to the risks associated with pHRT including age, the menopausal stage of the patient, the mode of delivery (e.g., transdermal versus oral), and delivered hormone dose. Another possible aspect is the presence of only one or two hormones (estrogen alone or in combination with progesterone) despite the complex cascade of hormones (e.g., inhibin, activin, testosterone) involved in the hypothalamus-pituitary-ovary (HPO) axis responsible for many aspects of a woman's physiological health. Our team has recently developed a cell-based hormone replacement therapy (cHRT) that can address several of these issues through a design in which two key ovarian cell types are in close proximity to each other as needed for ovarian hormone synthesis in native ovarian follicles. The cHRT constructs use a multilayer encapsulation technique to compartmentalize theca cells (TCs) and granulosa cells (GCs) to create a three-dimensional construct that mimics a native follicle structure. For these cHRT constructs, GCs are encapsulated in alginate, coated in poly-L-ornithine (PLO), then mixed with TCs in a 2nd layer of alginate. These biomimetic constructs have been shown to produce hormone concentrations similar to physiological levels both in vitro and in vivo. The implantation of such constructs, however, could be a regulatory challenge, so we are pursuing an ex vivo approach to production and characterization of the cell products. In this work, we are developing methods for the detection of ovarian hormones produced by the cHRT constructs by High Performance Liquid Chromatography with fluorescence detection (HPLC-FLD). Such techniques allow determination of ovarian hormone derivatives at low concentrations and that would be a better alternative to enzyme-linked immunosorbent assays.

Development of a bioreactor system in production of cell-based hormone replacement therapy through multilayer cell encapsulation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.