Bioengineered Ovarian Constructs to Prevent Osteoporosis in Rat Model of Ovarian Hormone Loss

Document Type

Conference Proceeding

Publication Date

11-9-2025

Publication Title

Tissue Eng Part A

Keywords

Cell Biology, Engineering, Materials Science

Abstract

Purpose/Objectives: Loss of ovarian hormones after menopause or other causes of ovarian failure leads to osteoporosis and bone fragility in women. Pharmacological hormone therapy (pHT) of estrogen alone or with progesterone attenuates postmenopausal bone loss, but it’s use declined due to cancer and cardiovascular risks. These limitations may arise due to the inability of pHT to fully participate in the hypothalamus-pituitary-ovary axis since pHT contains only one or two of the numerous hormones secreted by ovaries. To address this, we have developed a cell-based hormone therapy (cHT). Methodology: Female Fischer 344 rats (∼3 months old) were ovariectomized, and cHT constructs were implanted intraperitoneally seven weeks later. cHT constructs contained granulosa and theca cells from ∼3-week-old donor rat ovaries, encapsulated in alginate microcapsules with a perm- selective poly-L-ornithine coating. Two encapsulation strategies were employed: (1) a two-compartment system with granulosa cells in the inner and theca cells in the outer compartment for allogeneic (allogeneic cHT) and isogeneic (isogeneic cHT) cells from Wistar or Fischer donors, respectively; or (2) a one-compartment co-encapsulation system containing both isogeneic granulosa and theca cells (isogeneic co-encapsulation). Results: At 180 days post-implantation, average uterine weights (isogeneic cHT: 690 mg; allogeneic cHT: 530 mg; and isogeneic co-encapsulation: 566 mg), were not significantly different from age-matched ovary-intact controls (944 mg) but were significantly higher than ovariectomized controls (223 mg), suggesting maintenance of uterine health without hypertrophy. Micro-CT analysis of femoral bone revealed improved trabecular number in cHT groups (allogeneic cHT: 2.4 × 10⁻³ 1/µm; isogeneic cHT: 2.1 × 10⁻³ 1/µm; isogeneic co-encapsulation: 2.0 × 10⁻³ 1/µm) versus ovariectomized controls (7.5 × 10-4 1/µm), approaching age-matched levels (2.7 × 10⁻³ 1/µm). Improvements in trabecular spacing (allogeneic cHT: 487 μm; isogeneic cHT: 490 µm; isogeneic co-encapsulation: 494 μm; age-match: 303 μm; ovariectomy-only: 771 μm) and bone volume/total volume (allogeneic cHT: 25.8%, isogeneic cHT: 20.1%, isogeneic co-encapsulation: 21.3%, age-match: 28.3%, ovariectomy-only:16.1%) were also observed. Due to low sample size, bone data showed trends without statistical significance. Conclusion/Significance: The results suggest functional activity of cHT constructs up to 180 days and that allogeneic cells may be a suitable cell source. Ongoing studies will determine the biological and statistical significance of these findings.

Volume

31

Issue

23-24

First Page

e1348

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