Spermatogonial Differentiation Via Testicular Organoid

NCT ID: NCT06841861

Last Updated: 2025-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-28

Study Completion Date

2027-01-01

Brief Summary

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Purpose:

This clinical trial aims to explore the potential for human sperm production in vitro by sustaining a laboratory-cultured adult testicular environment. It also seeks to identify genetic factors contributing to human sterility and failed spermatogenesis. The study's primary objectives include:

1. Identifying genomic markers associated with sterility and failed spermatogenesis.
2. Developing an ex vivo (outside the body) testis "organ-on-a-chip" ("iTestis") to support stem cell cultivation.
3. Determining whether human spermatogenesis can be re-created in vitro using stem cells nurtured in the iTestis model.

Study Description:

Researchers will analyze the genomic profiles of fertile and sterile male participants to map genetic abnormalities associated with sterility. Using testicular and skin tissue samples from participants, spermatogonial stem cells and pluripotent stem cells will be isolated and utilized to construct the ex vivo iTestis. This system will integrate genomic insights and prior research to foster human spermatogenesis outside the body.

Participant Involvement:

Participants will provide the following samples:

* Blood sample for serum analysis.
* A skin tissue biopsy.
* Testicular tissue, obtained through fine needle aspiration (FNA) or testicular sperm extraction (TESE), as part of a routine procedure.

All procedures will be conducted by the principal investigator and qualified research staff, ensuring participant safety and adherence to ethical guidelines.

Detailed Description

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Conditions

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Infertility, Male Gene Abnormality Sterility, Male

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

All participants will be donating human tissue serum (blood), skin (via biopsy), and testicular tissue (via biopsy). These samples will be used for:

1. Primary cell culture of tissue cells will be established and genetic reprogramming could be applied to induce the long-term propagation of living cells.
2. Characterization and genetic screening of cells will be done to discover and reveal known or novel infertility-related biomarkers or genes.
3. Genetic reprogramming. Certain genes or gene products are inserted into donated cells to study how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.
4. Culture of cells in testicular organoids. Genetically unmodified or modified cells from donated samples could be placed in a laboratory-based testicular environment to see if sperm can be made.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Fertile Males

Fertile male participants (control group) with no known infertility conditions undergoing a vasectomy reversal. Participants will provide human tissue serum (via blood draw), skin (via biopsy), and testicular tissue (via biopsy).

Group Type ACTIVE_COMPARATOR

Stem cell

Intervention Type GENETIC

Primary cell cultures of tissue cells will be established. Cell cultures will undergo genetic reprogramming to induce the long-term propagation of living cells.

Genetic Screening

Intervention Type GENETIC

Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.

Genetic Reprogramming

Intervention Type GENETIC

Genes or gene products will be reinserted into cells to observe how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.

Cell Maturation

Intervention Type GENETIC

Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Infertile Males with Genetic Sterility: Sertoli Cell Only

Sterile male participants with unexplained or defined genetic infertility of sertoli cell only that are undergoing sperm mapping or testicular sperm retrieval (TESE) procedures. Participants will provide human tissue serum (via blood draw), skin (via biopsy), and testicular tissue (via biopsy).

Group Type EXPERIMENTAL

Stem cell

Intervention Type GENETIC

Primary cell cultures of tissue cells will be established. Cell cultures will undergo genetic reprogramming to induce the long-term propagation of living cells.

Genetic Screening

Intervention Type GENETIC

Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.

Genetic Reprogramming

Intervention Type GENETIC

Genes or gene products will be reinserted into cells to observe how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.

Cell Maturation

Intervention Type GENETIC

Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Infertile Males with Genetic Sterility: Early/Late Maturation Arrest

Sterile male participants with unexplained or defined genetic infertility of early to late maturation arrest that are undergoing sperm mapping or testicular sperm retrieval (TESE) procedures. Participant will provide human tissue serum (via blood draw), skin (via biopsy), and testicular tissue (via biopsy).

Group Type EXPERIMENTAL

Stem cell

Intervention Type GENETIC

Primary cell cultures of tissue cells will be established. Cell cultures will undergo genetic reprogramming to induce the long-term propagation of living cells.

Genetic Screening

Intervention Type GENETIC

Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.

Genetic Reprogramming

Intervention Type GENETIC

Genes or gene products will be reinserted into cells to observe how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.

Cell Maturation

Intervention Type GENETIC

Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Infertile Men with Acquired Sterility

Sterile male participants with acquired infertility from chemotherapy, infection, undecended testicles that are undergoing sperm mapping or testicular sperm retrieval (TESE) procedures. Participants will provide human tissue serum (via blood draw), skin (via biopsy), and testicular tissue (via biopsy).

Group Type EXPERIMENTAL

Stem cell

Intervention Type GENETIC

Primary cell cultures of tissue cells will be established. Cell cultures will undergo genetic reprogramming to induce the long-term propagation of living cells.

Genetic Screening

Intervention Type GENETIC

Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.

Genetic Reprogramming

Intervention Type GENETIC

Genes or gene products will be reinserted into cells to observe how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.

Cell Maturation

Intervention Type GENETIC

Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Interventions

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Stem cell

Primary cell cultures of tissue cells will be established. Cell cultures will undergo genetic reprogramming to induce the long-term propagation of living cells.

Intervention Type GENETIC

Genetic Screening

Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.

Intervention Type GENETIC

Genetic Reprogramming

Genes or gene products will be reinserted into cells to observe how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.

Intervention Type GENETIC

Cell Maturation

Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Intervention Type GENETIC

Other Intervention Names

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genome mapping genome characterization

Eligibility Criteria

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Inclusion Criteria

* Male sex of reproductive age (between 18 - 60 years old).
* Evidence of fertility or normal spermatogenesis.
* Will undergo study procedures in conjunction with their planned fertility or infertility procedures performed for clinical purposes.


* Male sex of reproductive age (between 18 - 60 years old).
* Males with evidence of \>1 year of infertility.
* Posesses diagnosis of azoospermia is on clinical evaluation.
* Will undergo study procedures in conjunction with their planned fertility or infertility procedures performed for clinical purposes.

Exclusion Criteria

\- The lack of diagnosis of fertility or infertility, and lack of testicles.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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The Turek Clinic, Inc

UNKNOWN

Sponsor Role collaborator

CellARTs Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul J Turek, MD

Role: PRINCIPAL_INVESTIGATOR

Chief Medical Officer

Locations

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The Turek Clinic

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Erica S Godart, BS

Role: CONTACT

4244579202

Constance John, PhD

Role: CONTACT

4153054888

Facility Contacts

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Paul J Turek, MD

Role: primary

4153923200

Lauren Massey, BSN

Role: backup

4153923200

References

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Ramathal C, Durruthy-Durruthy J, Sukhwani M, Arakaki JE, Turek PJ, Orwig KE, Reijo Pera RA. Fate of iPSCs derived from azoospermic and fertile men following xenotransplantation to murine seminiferous tubules. Cell Rep. 2014 May 22;7(4):1284-97. doi: 10.1016/j.celrep.2014.03.067. Epub 2014 May 1.

Reference Type BACKGROUND
PMID: 24794432 (View on PubMed)

Kee K, Pera RA, Turek PJ. Testicular germline stem cells. Nat Rev Urol. 2010 Feb;7(2):94-100. doi: 10.1038/nrurol.2009.263. Epub 2010 Jan 19.

Reference Type BACKGROUND
PMID: 20084076 (View on PubMed)

Kossack N, Meneses J, Shefi S, Nguyen HN, Chavez S, Nicholas C, Gromoll J, Turek PJ, Reijo-Pera RA. Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells. 2009 Jan;27(1):138-49. doi: 10.1634/stemcells.2008-0439.

Reference Type BACKGROUND
PMID: 18927477 (View on PubMed)

Walsh TJ, Pera RR, Turek PJ. The genetics of male infertility. Semin Reprod Med. 2009 Mar;27(2):124-36. doi: 10.1055/s-0029-1202301. Epub 2009 Feb 26.

Reference Type BACKGROUND
PMID: 19247914 (View on PubMed)

Durruthy-Durruthy J, Briggs SF, Awe J, Ramathal CY, Karumbayaram S, Lee PC, Heidmann JD, Clark A, Karakikes I, Loh KM, Wu JC, Hoffman AR, Byrne J, Reijo Pera RA, Sebastiano V. Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions. PLoS One. 2014 Apr 9;9(4):e94231. doi: 10.1371/journal.pone.0094231. eCollection 2014.

Reference Type BACKGROUND
PMID: 24718618 (View on PubMed)

Kogut I, McCarthy SM, Pavlova M, Astling DP, Chen X, Jakimenko A, Jones KL, Getahun A, Cambier JC, Pasmooij AMG, Jonkman MF, Roop DR, Bilousova G. High-efficiency RNA-based reprogramming of human primary fibroblasts. Nat Commun. 2018 Feb 21;9(1):745. doi: 10.1038/s41467-018-03190-3.

Reference Type BACKGROUND
PMID: 29467427 (View on PubMed)

Durruthy JD, Sebastiano V. Derivation of GMP-compliant integration-free hiPSCs using modified mRNAs. Methods Mol Biol. 2015;1283:31-42. doi: 10.1007/7651_2014_124.

Reference Type BACKGROUND
PMID: 25304205 (View on PubMed)

Huang P, Zhu J, Liu Y, Liu G, Zhang R, Li D, Pei D, Zhu P. Identification of New Transcription Factors that Can Promote Pluripotent Reprogramming. Stem Cell Rev Rep. 2021 Dec;17(6):2223-2234. doi: 10.1007/s12015-021-10220-z. Epub 2021 Aug 26.

Reference Type BACKGROUND
PMID: 34448118 (View on PubMed)

Gaur M, Ramathal C, Reijo Pera RA, Turek PJ, John CM. Isolation of human testicular cells and co-culture with embryonic stem cells. Reproduction. 2018 Feb;155(2):153-166. doi: 10.1530/REP-17-0346.

Reference Type BACKGROUND
PMID: 29326135 (View on PubMed)

Chui K, Trivedi A, Cheng CY, Cherbavaz DB, Dazin PF, Huynh AL, Mitchell JB, Rabinovich GA, Noble-Haeusslein LJ, John CM. Characterization and functionality of proliferative human Sertoli cells. Cell Transplant. 2011;20(5):619-35. doi: 10.3727/096368910X536563. Epub 2010 Nov 5.

Reference Type BACKGROUND
PMID: 21054948 (View on PubMed)

Bouyer C, Chen P, Guven S, Demirtas TT, Nieland TJ, Padilla F, Demirci U. A Bio-Acoustic Levitational (BAL) Assembly Method for Engineering of Multilayered, 3D Brain-Like Constructs, Using Human Embryonic Stem Cell Derived Neuro-Progenitors. Adv Mater. 2016 Jan 6;28(1):161-7. doi: 10.1002/adma.201503916. Epub 2015 Nov 10.

Reference Type BACKGROUND
PMID: 26554659 (View on PubMed)

Calamak S, Ermis M, Sun H, Islam S, Sikora M, Nguyen M, Hasirci V, Steinmetz LM, Demirci U. A Circulating Bioreactor Reprograms Cancer Cells Toward a More Mesenchymal Niche. Adv Biosyst. 2020 Feb;4(2):e1900139. doi: 10.1002/adbi.201900139. Epub 2020 Jan 14.

Reference Type BACKGROUND
PMID: 32293132 (View on PubMed)

Ishii T, Pera RA. Creating human germ cells for unmet reproductive needs. Nat Biotechnol. 2016 May 6;34(5):470-3. doi: 10.1038/nbt.3559. No abstract available.

Reference Type BACKGROUND
PMID: 27153270 (View on PubMed)

Ramathal C, Angulo B, Sukhwani M, Cui J, Durruthy-Durruthy J, Fang F, Schanes P, Turek PJ, Orwig KE, Reijo Pera R. DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs. Sci Rep. 2015 Oct 12;5:15041. doi: 10.1038/srep15041.

Reference Type BACKGROUND
PMID: 26456624 (View on PubMed)

Durruthy Durruthy J, Ramathal C, Sukhwani M, Fang F, Cui J, Orwig KE, Reijo Pera RA. Fate of induced pluripotent stem cells following transplantation to murine seminiferous tubules. Hum Mol Genet. 2014 Jun 15;23(12):3071-84. doi: 10.1093/hmg/ddu012. Epub 2014 Jan 20.

Reference Type BACKGROUND
PMID: 24449759 (View on PubMed)

Medrano JV, Pera RA, Simon C. Germ cell differentiation from pluripotent cells. Semin Reprod Med. 2013 Jan;31(1):14-23. doi: 10.1055/s-0032-1331793. Epub 2013 Jan 17.

Reference Type BACKGROUND
PMID: 23329632 (View on PubMed)

Other Identifiers

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SDTO 1

Identifier Type: -

Identifier Source: org_study_id

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