Spermatogonial Differentiation Via Testicular Organoid

Официальное название

A Study of Therapeutic Spermatogonial Differentiation for Infertile Men Via Testicular Organoid

Обзор

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.

Вмешательства

• Генная терапия 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.
• Генная терапия Genetic Screening
  Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.
• Генная терапия 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.
• Генная терапия Cell Maturation
  Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.

Первичные конечные точки

• Successful derivation of patient-specific human spermatogonial stem cells (hSSCs) from testicular tissue samples. [Срок оценки: From initial sample collection to 24 months post all subject sample collection completion]

Критерии участия

Inclusion Criteria: Group 1 (Fertile Control)

• 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.

Inclusion Criteria: Group 2 and 3 (Infertile)

• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• The Turek Clinic — San Francisco

Публикации

• 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. PMID 24794432
• 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. PMID 20084076
• 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. PMID 18927477
• 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. PMID 19247914
• 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. PMID 24718618
• 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. PMID 29467427
• 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. PMID 25304205
• 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. PMID 34448118

Идентификаторы

NCT: NCT06841861 · SDTO 1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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