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| Name | Class |
|---|---|
| The Turek Clinic, Inc | UNKNOWN |
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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:
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:
All procedures will be conducted by the principal investigator and qualified research staff, ensuring participant safety and adherence to ethical guidelines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fertile Males | Active Comparator | 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). |
|
| Infertile Males with Genetic Sterility: Sertoli Cell Only | Experimental | 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). |
|
| Infertile Males with Genetic Sterility: Early/Late Maturation Arrest | Experimental | 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). |
|
| Infertile Men with Acquired Sterility | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stem cell | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Successful derivation of patient-specific human spermatogonial stem cells (hSSCs) from testicular tissue samples. | Metric: The presence of viable hSSCs characterized by specific molecular and cellular markers (e.g., GFRα1, PLZF) within a predefined timeframe post-derivation. Assessment Method: Flow cytometry, immunohistochemistry, or RT-PCR to confirm marker expression. | From initial sample collection to 24 months post all subject sample collection completion |
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| Measure | Description | Time Frame |
|---|---|---|
| Development and functional validation of an ex vivo testis organ-on-a-chip ('iTestis') platform for the cultivation and maintenance of isolated spermatogonial stem cells (hSSCs) | Metric: Successful development of a biomimetic iTestis capable of maintaining hSSCs in a viable and undifferentiated state over a predefined culture period. Assessment Method: Viability: Measured by live/dead assays or metabolic activity (e.g., MTT or ATP assays). Stemness: Expression of hSSC markers (e.g., GFRα1, PLZF) using immunofluorescence or qRT-PCR. |
Inclusion Criteria: Group 1 (Fertile Control)
Inclusion Criteria: Group 2 and 3 (Infertile)
Exclusion Criteria:
- The lack of diagnosis of fertility or infertility, and lack of testicles.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Erica S Godart, BS | Contact | 4244579202 | ericagodart@gmail.com | |
| Constance John, PhD | Contact | 4153054888 | connie.john@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Paul J Turek, MD | Chief Medical Officer | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Turek Clinic | Recruiting | San Francisco | California | 94108 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24794432 | Background | 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. | |
| 20084076 | Background |
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| ID | Term |
|---|---|
| D007248 | Infertility, Male |
| ID | Term |
|---|---|
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007246 | Infertility |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| D002874 | Chromosome Mapping |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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All participants will be donating human tissue serum (blood), skin (via biopsy), and testicular tissue (via biopsy). These samples will be used for:
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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).
|
| Genetic Screening | Genetic | Serum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes. |
|
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| Genetic Reprogramming | 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 | Genetic | Genetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity. |
|
| From the date of the first successful derivation of patient-specific hSSCs until an ex vivo testis platform is developed and can functionally cultivate and maintain the isolated spermatogonial stem cells (hSSCs), assessed for up to 24 months. |
| Promotion of human spermatogenesis in vitro ('iSperm') using hSSCs and hiPSCs within the iTestis platform. | Metric: Generation of haploid spermatogenic cells (e.g., spermatocytes, spermatids, or sperm-like cells) from hSSCs and/or hiPSCs cultured within the iTestis platform. Assessment Method: Flow cytometry or fluorescence-activated cell sorting (FACS) to confirm haploid cell production (e.g., 1N DNA content). Gene and protein expression analysis of spermatogenic markers (e.g., SCP3, acrosin, protamine 1) using RT-PCR and immunofluorescence. | From the date of the initial development of the ex vivo testis platform until the promotion of human spermatogenesis using hSSCs and hiPSCs is achieved within the iTestis platform, assessed for up to 24 months. |
| Successful derivation of patient-specific induced pluripotent stem cells (hiPSCs) from skin samples. | Metric: Generation of hiPSCs that exhibit hallmark pluripotency characteristics from participant skin fibroblasts. Assessment Method: Morphological Analysis: Observation of colony morphology consistent with hiPSCs. Molecular and Functional Validation: Expression of key pluripotency markers (e.g., OCT4, SOX2, NANOG) verified by immunofluorescence, qRT-PCR, or flow cytometry. Functional pluripotency confirmed via in vitro differentiation into the three germ layers (endoderm, mesoderm, ectoderm). | From initial sample collection to 24 months post all subject sample collection completion. |
| 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. |
| 18927477 | Background | 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. |
| 19247914 | Background | 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. |
| 24718618 | Background | 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. |
| 29467427 | Background | 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. |
| 25304205 | Background | 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. |
| 34448118 | Background | 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. |
| 29326135 | Background | 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. |
| 21054948 | Background | 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. |
| 26554659 | Background | 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. |
| 32293132 | Background | 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. |
| 27153270 | Background | 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. |
| 26456624 | Background | 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. |
| 24449759 | Background | 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. |
| 23329632 | Background | 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. |
| D052801 |
| Male Urogenital Diseases |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |