# Immuno-Isolating capsule for delivery of cell-based therapy for restoration of ovarian endocrine function in an animal model

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $675,370

## Abstract

Premature ovarian insufficiency (POI) is a common complication of anticancer treatments, such as
chemotherapy and bone marrow transplantation, due to treatment toxicity. In female cancer survivors
POI causes sterility, and loss of the ovarian endocrine function, which in turn results in premature
osteopenia, muscle wasting, and accelerated cardiovascular disease. These long-lasting effects are
significant, particularly for young girls reaching puberty. Our results in an ovariectomized adult mouse
model have demonstrated that transplantation of an ovarian allograft encapsulated in an
immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function
without eliciting immune rejection. Yet, rodents present limitations for clinical translation to humans,
such as 1) the small size of a prepubertal female limits intervention before puberty and onset of puberty
is regulated differently in primates than in rodents; 2) the small size and multiovulatory character of the
mouse ovaries have a limited translational potential; and 3) the differences in immune response limit the
reach of our findings. To overcome these challenges and increase the translational potential, we propose
to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of
encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs, we will study the
longevity of graft function as well as the dynamics of the recipient’s immune response to initial and
repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian
endocrine function in young women with POI.
We have demonstrated in an ovariectomized adult mouse model that implantation of an ovarian allograft
encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine
ovarian function without eliciting immune rejection. Yet, rodents present limitations for clinical
translation to humans, such as the small size of a prepubertal female, which limits intervention before
puberty and the differences in allo-immune response between rodents and humans.
The proposed research To overcome these challenges and increase the translational potential, we
propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the
efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs, we will
study the longevity of graft function as well as the dynamics of the recipient’s immune response to initial
and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian
endocrine function in young women with POI.

## Key facts

- **NIH application ID:** 10519128
- **Project number:** 1R01HD105018-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ariella Shikanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $675,370
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519128

## Citation

> US National Institutes of Health, RePORTER application 10519128, Immuno-Isolating capsule for delivery of cell-based therapy for restoration of ovarian endocrine function in an animal model (1R01HD105018-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10519128. Licensed CC0.

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