Stem Cell Therapy for Male Infertility

(SDTO Trial)

Overseen By Constance John, PhD

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: CellARTs Inc.

Disqualifiers: Lack of testicles, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores using stem cells to create sperm in a lab setting to assist men with fertility issues. The researchers aim to understand the genetic causes of male infertility and determine if sperm can be grown outside the body using a specialized lab device. Men who have experienced difficulty fathering a child for over a year and have been diagnosed with no sperm production may be suitable candidates for this study. Participants will provide blood, skin, and testicular samples to aid the research. As a Phase 1/Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stem cell treatments for male infertility are generally safe and well-tolerated. Trials have reported a good safety record, with no common serious side effects. Studies indicate that these treatments rarely cause severe problems. However, like any treatment, some risks exist. Specifically, there is a small chance of developing certain types of cancer, though this risk remains low.

The genetic screening used in these therapies is also considered safe. It identifies genetic issues without causing harm. Past research has not reported any major safety concerns from these procedures.

Overall, available data suggests these treatments are generally safe for patients. Since this study is in the early stages, ongoing trials will provide more detailed safety information. Participants receive close monitoring to ensure their safety and to quickly address any issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they use stem cell therapy to address male infertility, offering a groundbreaking approach compared to traditional methods like hormone treatments or surgery. This therapy involves genetic reprogramming and screening, which could potentially regenerate sperm-producing cells in men with genetic or acquired sterility. Unlike standard treatments that often focus on managing symptoms or facilitating sperm retrieval, this method aims to restore natural fertility by targeting the root cause of infertility at the cellular level. This innovative approach holds promise for providing a lasting solution for men who have limited options with current treatments.

What evidence suggests that this trial's treatments could be effective for male infertility?

Research has shown promising new ways to treat male infertility using advanced techniques. This trial will explore different approaches, including genetic reprogramming, genetic screening, and stem cell therapy, to assist men who have trouble producing sperm. Early results from previous studies suggest these methods might correct genetic problems affecting sperm production. Additionally, genetic testing has become more precise, helping to pinpoint the exact genetic issues causing infertility. Although these methods remain in the early stages, they offer hope for new treatments for men with both genetic and acquired infertility. Participants in this trial will be divided into groups, including those with genetic sterility and those with acquired sterility, to evaluate the effectiveness of these innovative approaches. ^{1 2 3 6 7}

Who Is on the Research Team?

Paul J Turek, MD

Principal Investigator

Chief Medical Officer

Are You a Good Fit for This Trial?

This trial is for men experiencing infertility due to genetic abnormalities or failed spermatogenesis. Participants will provide blood, skin tissue, and testicular tissue samples. The study excludes details on specific inclusion and exclusion criteria.

Inclusion Criteria

I am a man aged 18-60 with a diagnosis of no sperm count and have been infertile for over a year.

I am a man aged 18-60 with normal fertility undergoing fertility procedures.

Exclusion Criteria

I have not been diagnosed with fertility issues and I do not have testicles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection

Participants provide blood, skin, and testicular tissue samples for analysis

1-2 weeks

1 visit (in-person)

Ex Vivo Testis Development

Development of the iTestis platform using participant-derived stem cells

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after sample collection and iTestis development

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Genetic Reprogramming
• Genetic Screening
• Stem cell

Trial Overview The trial investigates human sperm production in vitro using an 'iTestis' organ-on-a-chip model. It involves genetic screening of participants, stem cell isolation from tissues provided, and attempts to recreate spermatogenesis outside the body.

How Is the Trial Designed?

Group I: Infertile Men with Acquired Sterility Experimental Treatment 4 Interventions

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 II: Infertile Males with Genetic Sterility: Sertoli Cell Only Experimental Treatment 4 Interventions

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 III: Infertile Males with Genetic Sterility: Early/Late Maturation Arrest Experimental Treatment 4 Interventions

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 IV: Fertile Males Active Control 4 Interventions

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).

Who Is Running the Clinical Trial?

CellARTs Inc.

Lead Sponsor

Trials

1

Recruited

100+

The Turek Clinic, Inc

Collaborator

Trials

1

Recruited

100+

Published Research Related to This Trial

Pluripotent stem cells (PSCs) have the potential to differentiate into any cell type, including male germ cells, which could lead to new treatments for male infertility.

Current methods for producing functional sperm from PSCs include in vitro differentiation and in vivo transplantation, offering a promising source of autologous gametes for infertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retracted article: In vitro derivation of mammalian germ cells from stem cells and their potential therapeutic application. Saito, S., Lin, YC., Murayama, Y., et al.[2019]

Emerging reproductive technologies, such as using immature sperm precursors like spermatids and secondary spermatocytes, have shown promise in fertilizing human oocytes and resulting in healthy babies, offering hope for infertile couples.

While these innovative methods could provide alternative sources of gametes, their safety must be thoroughly established before being applied in human treatments, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative sources of gametes: reality or science fiction? Tsai, MC., Takeuchi, T., Bedford, JM., et al.[2022]

Embryonic stem cell (ESC)-derived models show promise for screening male reproductive toxicity, as they closely resemble primordial germ cells and can be differentiated into gametes, providing a valuable tool for understanding infertility causes.

Human ESC (hESC) are suggested to be more effective than mouse ESC for in vitro toxicity screening due to their closer similarity to human gamete development, which could lead to better insights into environmental impacts on male reproductive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of human embryonic stem cell-based models for male reproductive toxicity screening. Krtolica, A., Giritharan, G.[2014]

A study on testicular cells from men with obstructive azoospermia found that culturing spermatogonial stem cells (SSCs) in a testicular cell suspension significantly increased colony formation compared to other culture methods, indicating a more effective environment for cell growth.

The testicular cell suspension culture also led to higher expression of germ cell-specific genes while reducing pluripotency gene expression, suggesting that this method promotes the differentiation of SSCs into functional gametes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Epigenetic Assessment of Human Spermatogenic Cells Derived from Obstructive Azoospermic Patients in Different Culture Systems. Zahiri, M., Movahedin, M., Mowla, SJ., et al.[2021]

Spermatogonial stem cells (SSCs) are unique to males and are crucial for producing sperm and passing on genetic information, with the ability to self-renew and differentiate throughout a male's life.

A transplantation technique allows SSCs from fertile males to restore fertility in infertile males, and research indicates that the growth factors needed for SSC self-renewal are likely similar across mammalian species, paving the way for potential human applications in assisted reproduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technology insight: In vitro culture of spermatogonial stem cells and their potential therapeutic uses. Kubota, H., Brinster, RL.[2022]

Stem cell transplantation has been shown to effectively treat azoospermia, a major cause of male infertility, based on a systematic review of 18 studies, indicating its potential as a therapeutic option in animal models.

Among different methods, xenotransplantation and the use of umbilical cord mesenchymal stem cells were particularly effective, enhancing the expression of key meiosis-related genes and promoting spermatogenesis, although further research is needed to confirm these findings in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Cellular Therapy for Azoospermia in Animal Models: A Systematic Review and Meta-Analysis. Qiu, J., Ma, H., Pei, Y.[2023]

A new transgenic rat model expressing EGFP in spermatogonial stem cells (SSCs) allows for easy identification and isolation of these cells, which are crucial for male fertility and spermatogenesis.

The DDX4-EGFP rat model demonstrated that SSCs can successfully establish spermatogenesis in infertile mouse testes, highlighting its potential for studying male infertility and germline modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DDX4-EGFP transgenic rat model for the study of germline development and spermatogenesis. Gassei, K., Sheng, Y., Fayomi, A., et al.[2018]

Human Sertoli cells can be reprogrammed into male germline stem cells (SSCs) by overexpressing specific factors (DAZL, DAZ2, and BOULE), demonstrating a new method for generating male gametes.

The derived SSCs not only showed the ability to proliferate and differentiate into mature sperm cells in vitro but also maintained normal chromosomes, indicating a high safety profile for potential use in treating male infertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct reprogramming of human Sertoli cells into male germline stem cells with the self-renewal and differentiation potentials via overexpressing DAZL/DAZ2/BOULE genes. Zhang, W., Chen, W., Cui, Y., et al.[2022]

The study demonstrated that mouse bone marrow-derived mesenchymal stem cells (BMSCs) can be differentiated into male germ-like cells when co-cultured with testicular cells and treated with bone morphogenetic protein 4 (BMP4), indicating a potential new approach for treating azoospermia.

Specifically, the treatment group that involved indirect co-culture with testicular cells showed a significant increase in the expression of male germ-like genes, suggesting that testicular cells release factors that aid in this differentiation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation of bone marrow derived mesenchymal stem cells into male germ-like cells in co-culture with testicular cells. Malekmohamadi, N., Abdanipour, A., Ghorbanlou, M., et al.[2020]

Infertility affects not just the ability to have children but also has broader emotional and societal impacts, highlighting the importance of addressing this condition.

The review discusses promising stem cell and gene therapy methods currently being researched that could provide new fertility treatment options for men with azoospermia, a condition where no sperm is produced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental methods to preserve male fertility and treat male factor infertility. Gassei, K., Orwig, KE.[2018]

Chemotherapy and radiotherapy can cause permanent infertility in over 4000 male patients annually in the U.S. due to damage to the gonads, highlighting the need for effective fertility preservation methods.

Spermatogonial stem cells (SSCs) found in the testes of prepubescent boys may offer a promising avenue for restoring fertility, and the proposal of allogeneic testicular stem cell transplantation with an encapsulation device aims to develop a feasible solution for patients unable to produce functional sperm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surrogate testes: Allogeneic spermatogonial stem cell transplantation within an encapsulation device may restore male fertility. Gül, M., Dong, L., Wang, D., et al.[2021]

In a study involving rat models, researchers successfully restored fertility in DAZL-deficient rats by transplanting as few as 50,000 cultured spermatogonial stem cells, achieving 100% germline transmission to offspring.

This research suggests that similar techniques could potentially be applied to humans, offering hope for treating male infertility caused by genetic mutations or other factors, using minimal testis biopsies to obtain functional stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sterile testis complementation with spermatogonial lines restores fertility to DAZL-deficient rats and maximizes donor germline transmission. Richardson, TE., Chapman, KM., Tenenhaus Dann, C., et al.[2021]

This study successfully generated functional spermatids from cryptorchid patients, which is crucial for treating male infertility, particularly in azoospermia cases.

The treatment with retinoic acid and stem cell factor significantly enhanced the development of spermatogonial stem cells, leading to haploid spermatids that have the potential for fertilization and embryo development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of haploid spermatids with fertilization and development capacity from human spermatogonial stem cells of cryptorchid patients. Yang, S., Ping, P., Ma, M., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8577253/

Rescue of male infertility through correcting a genetic ... Our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0015028225004339

Male fertility restoration with stem cell–based therapies This review examines the landscape of emerging stem cell–based therapies for overcoming an infertility diagnosis, with particular emphasis on strategies using ...

3. withpower.com withpower.com/trial/phase-2-infertility-male-2-2024-33321

Stem Cell Therapy for Male Infertility (SDTO Trial) ... Screening and Stem cell will have tolerable side effects & efficacy for patients with Male Infertility, Genetic Abnormality, Male Sterility and Male Infertility

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8651766/

Update on genetic screening and treatment for infertile men ... In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic ...

5. fertstert.org fertstert.org/article/S0015-0282(25)00162-1/fulltext

Genetic syndromes leading to male infertility: a systematic ... The goal of this article is to provide an overview of each clinical condition, including genetic mechanisms, with an emphasis on male infertility manifestations ...

6. mensreproductivehealth.com mensreproductivehealth.com/the-future-of-male-fertility-stem-cells-and-exosomes-for-non-obstructive-azoospermia/

THE FUTURE OF MALE FERTILITY: STEM CELLS AND ... Safety considerations: Thus far, MSC therapies for male infertility have been reported to have a good safety profile. In the trials ...

7. mdpi.com mdpi.com/2073-4409/14/21/1660

Safety Assessment of Stem Cell-Based Therapies This comprehensive analysis assesses the potential risk of oncological disease development associated with cell therapy. Stem cell–derived extracellular ...