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Ex vivo whole ovary culture system for screening gonadotoxicity during drug development

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HD114386-01
Agency Tracking Number: R43HD114386
Amount: $309,251.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NICHD
Solicitation Number: PA22-176
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-22
Award End Date (Contract End Date): 2024-08-31
Small Business Information
4401 LEEDS AVE STE 130
North Charleston, SC 29405-7554
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (913) 940-0673
Business Contact
Phone: (612) 567-2723
Research Institution

Background: In the U.S., over 200,000 girls and women age 0-49 are diagnosed with cancer annually. While
improved diagnosis and treatment have led to increased survival rates (75% in premenopausal and 85% in
childhood cancer patients), devastating side effects of cancer therapies include premature ovarian failure,
infertility and menopause-related health risks. The current industrial standard for detecting and de-risking
ovotoxicity is to use in vivo rodent models or 2D/3D in vitro ovarian cells/tissue culture with significant drawbacks.
This Phase I proposal aims to develop an ex vivo system for long-term assessment of ovarian damage at
morphological, functional, and molecular levels, in a whole ovary model.
Approach: The objectives for this Phase I SBIR proposal are to 1) build a novel ex vivo microfluidic organ
perfusion device that will support culture of whole ovaries for 7 days and establish optimal culture conditions, as
well as to 2) test this culture system using a chemotherapy medication, 4-hydroperoxy cyclophosphamide, a
metabolite from one of the most commonly used drugs, cyclophosphamide. Endpoints will include the ability of
oocytes to mature in vitro, as well as protein and RNA expression of markers that demonstrate follicular health
and apoptosis. The resultant technology of this project will be the first perfusion unit designed for the whole
ovary of large mammals (including humans) and can control perfusion pressure, flow rate and treatment
concentration with a build-in feedback mechanism to maintain constant pressure during perfusion.
Future Directions and Commercialization potential: This phase I project will provide crucial proof-of-principle
for future Phase II studies to test the ability of the whole ovary culture system for longer culture period (1 month),
collaborate with drug companies to screen drug candidates for their ovotoxicity or ovoprotection potentials, and
to examine long-term endocrine and fertility consequences by transplanting chemotherapeutics-treated ovaries
back to the host animal. The technology to maintain prolonged live/functional has the added potential for
observing follicle maturation and its related studies (basic and clinical research). Successful development of an
ex vivo whole ovary culture system will set new industrial standards during drug development because it will
allow the use of ovaries from larger mammals (including women) without causing harm and death to the animal,
and it will allow evaluation of the whole ovary while mimicking in vivo delivery of toxic chemotherapeutics.

* Information listed above is at the time of submission. *

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