In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure

Sivanandane Sittadjody, Justin M. Saul, John P. McQuilling, Sunyoung Joo, Thomas C. Register, James J. Yoo, Anthony Atala and Emmanuel C. Opara ()
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Sivanandane Sittadjody: Wake Forest School for Medicine
Justin M. Saul: Paper and Biomedical Engineering, Miami University
John P. McQuilling: Wake Forest School for Medicine
Sunyoung Joo: Wake Forest School for Medicine
Thomas C. Register: Wake Forest University School of Medicine
James J. Yoo: Wake Forest School for Medicine
Anthony Atala: Wake Forest School for Medicine
Emmanuel C. Opara: Wake Forest School for Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Safe clinical hormone replacement (HR) will likely become increasingly important in the growing populations of aged women and cancer patients undergoing treatments that ablate the ovaries. Cell-based HRT (cHRT) is an alternative approach that may allow certain physiological outcomes to be achieved with lower circulating hormone levels than pharmacological means due to participation of cells in the hypothalamus-pituitary-ovary feedback control loop. Here we describe the in vivo performance of 3D bioengineered ovarian constructs that recapitulate native cell–cell interactions between ovarian granulosa and theca cells as an approach to cHRT. The constructs are fabricated using either Ca++ or Sr++ to crosslink alginate. Following implantation in ovariectomized (ovx) rats, the Sr++-cross-linked constructs achieve stable secretion of hormones during 90 days of study. Further, we show these constructs with isogeneic cells to be effective in ameliorating adverse effects of hormone deficiency, including bone health, uterine health, and body composition in this rat model.

Date: 2017
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DOI: 10.1038/s41467-017-01851-3

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