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Derivation of Functional Spermatogonia Stem Cells from Rhesus Macaque iPSCs

Award Number: R01OD028223
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/09/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Derivation of Functional Spermatogonia Stem Cells from Rhesus Macaque iPSCs - Summary Currently, ~15% of couples worldwide and ~12% of men in the United States are subfertile or infertile. Some root causes for this infertility lie in genetic defects, but others are due to exposure to industrial and environmental toxicants, injury, or medical treatments such as alkylating chemotherapies which almost always result in sterility, especially in men. Male pre-pubertal cancer patients are especially at risk since they are unable to provide a semen sample prior to their cancer treatments. Fertility preservation in pre-pubertal pediatric cancer patients is an emerging and ever-evolving field. However treatment options are limited. Since 1980, Assisted Reproductive Technology (ART) has gained worldwide acceptance and Intracytoplasmic Sperm Injection (ICSI) has since aided couples with severe infertility to achieve pregnancies. However, these advanced techniques require the production of even a small amount of functional gametes. For those individuals rendered sterile by non-genetic root causes unable to produce gametes, such as pediatric cancer survivors, there are no cures for their infertility. As the incidences of pediatric cancers, including testicular and germ cell cancers, continue to rise, there is a need for the development of novel stem-cell based therapies to treat male factor infertility in patients rendered sterile by medical treatments. Patient-specific pluripotent stem cells represent one future potential source to restore fertility by generating germline precursors such as spermatogonial stem cells (SSCs) in vitro that can restore fertility in vivo following transplantation. This therapeutic approach would allow infertile men to produce offspring with their partners without having to use advanced reproductive technologies such as ICSI. Our team has pioneered the ability to transplant autologous and donor rhesus SSCs into recipient rhesus testes to re- colonize the testis and restore fertility. Additionally, our group was the first group to derive SSC-like cells from human induced pluripotent stem cells (iPSCs). Here, we hypothesize that NHP iPSC-derived SSCs can be transplanted into sterilized autologous recipient testes to restore fertility. Furthermore, we hypothesize that sperm generated from transplanted recipients can produce healthy embryos and offspring. This proposal under PAR- 16-093 Improvement of Animal Models for Stem Cell-based Regenerative Medicine (R01) will determine, using a non-human primate stem cell model, whether iPSCs can be utilized to treat male factor infertility.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$15,000 )
2025	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	000	4	10/23/2024	NON-COMPETING CONTINUATION	-$15,000
														Subtotal = -$15,000

Issue Date FY: 2022 ( Subtotal = $1,209,251 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	000	4	6/14/2022	NON-COMPETING CONTINUATION	$709,362
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	001	4	6/15/2022	SUPPLEMENT FOR EXPANSION	$499,889
														Subtotal = $1,209,251

Issue Date FY: 2021 ( Subtotal = $712,382 )
2021	2021	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	000	3	6/10/2021	NON-COMPETING CONTINUATION	$712,382
														Subtotal = $712,382

Issue Date FY: 2020 ( Subtotal = $732,832 )
2020	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	000	2	6/9/2020	NON-COMPETING CONTINUATION	$732,832
														Subtotal = $732,832

Issue Date FY: 2019 ( Subtotal = $773,131 )
2019	2019	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Research Infrastructure Programs	000	1	9/9/2019	NEW	$773,131
														Subtotal = $773,131

Grand Total All Awards = $3,412,596

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Derivation of Functional Spermatogonia Stem Cells from Rhesus Macaque iPSCs

Award Number: R01OD028223

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/09/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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