Spermatogonial Differentiation Via Testicular Organoid
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexMale
Age18-60
SponsorCellARTs Inc.
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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).
Disqualifiers
None
Trial design
Design model
Single group
Treatments tested in this trial
Stem cell
GeneticPrimary 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
GeneticSerum samples are processed through RNA sequencing to reveal known and novel infertility-related biomarkers and genes.
Genetic Reprogramming
GeneticGenes 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
GeneticGenetically unmodified and modified cells are placed in a laboratory-based testicular environment to promote spermatogenesis into maturity.
Treatment groups
100 Participants
are divided into 4 treatment groupsGroup A: Fertile MalesActive comparator 4 interventions
Group B: Infertile Males with Genetic Sterility: Sertoli Cell OnlyExperimental treatment 4 interventions
Group C: Infertile Males with Genetic Sterility: Early/Late Maturation ArrestExperimental treatment 4 interventions
Group D: Infertile Men with Acquired SterilityExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
From initial sample collection to 24 months post all subject sample collection completionOther outcomes
1
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.
Time frame
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.2
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.
Time frame
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.3
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).
Time frame
From initial sample collection to 24 months post all subject sample collection completion.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
CellARTs Inc.
Lead sponsor
The Turek Clinic, Inc
Collaborator
Source ClinicalTrials.gov