SSC Transplant + Testicular Tissue Grafting for Male Infertility

Overseen By Jennifer L Anglin

Age: Any Age

Sex: Male

Trial Phase: Academic

Sponsor: University of Pittsburgh

Disqualifiers: Leukemia, Lymphoma, Testicular cancer, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test new methods to help men who have become infertile after cancer treatments like chemotherapy or radiation. It employs two techniques: transplanting spermatogonial stem cells (early-stage sperm cells) and grafting testicular tissue to restore fertility. Men who stored their testicular tissue before undergoing such treatments and are now healthy enough for the procedure might be suitable candidates.

As an unphased trial, this study offers participants a unique opportunity to contribute to pioneering research that could restore fertility for many.

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.

What prior data suggests that these transplant technologies are safe for restoring fertility?

Research has shown that spermatogonial stem cell transplantation and testicular tissue grafting have promising safety results in early studies. In animal tests with mice and primates, these treatments were well-tolerated. Specifically, studies found that transplanted stem cells successfully restarted sperm production without causing major problems or harm to the animals.

While these results are encouraging, human trials are necessary to fully assess their safety and effectiveness in people. As this study is in the early stages, it primarily focuses on testing the safety of these methods for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about spermatogonial stem cell (SSC) transplantation and testicular tissue grafting for male infertility because these approaches offer a novel way to restore fertility. Unlike standard treatments like hormone therapy or assisted reproductive technologies, SSC transplantation directly targets and replenishes the cells responsible for sperm production. Testicular tissue grafting complements this by creating a supportive environment for these stem cells to mature and function effectively. This combination could potentially address the root cause of infertility rather than just managing symptoms, offering new hope for men struggling with this condition.

What evidence suggests that spermatogonial stem cell transplant and testicular tissue grafting might be effective for male infertility?

Research has shown that certain techniques can help restore fertility. In studies with animals like mice and primates, methods such as spermatogonial stem cell (SSC) transplantation and testicular tissue grafting have successfully restarted sperm production. For instance, in primates treated with a drug called busulfan, transplanted SSCs produced sperm capable of fertilizing eggs. This trial will investigate the effectiveness of SSC transplantation and testicular tissue grafting in humans. These encouraging results suggest that these techniques might effectively treat infertility, especially for younger males who have stored their testicular tissue before undergoing treatments that could harm fertility. While more research is needed in humans, these methods have proven successful in animals. ^{1 2 3 5 6}

Who Is on the Research Team?

Kyle E Orwig, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for males who have frozen their testicular tissue before undergoing treatments that could cause infertility, like chemotherapy or radiation. They must be healthy enough for anesthesia and past Tanner stage 3 of puberty. Those with a history of certain cancers or conditions affecting consent are not eligible.

Inclusion Criteria

I have my testicular tissue/cells stored for future use due to a treatment that could cause infertility.

My doctor has approved me for a stem cell transplant after finishing my primary treatment.

I am healthy enough to be put under anesthesia.

Exclusion Criteria

I have a history of leukemia, lymphoma, testicular cancer, or cancer that affected my testicles.

You have a mental or emotional condition that stops you from fully understanding the study and giving informed consent.

I am at high risk for complications if I undergo surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo spermatogonial stem cell transplantation and testicular tissue grafting

3 months

Follow-up

Participants are monitored for return of spermatogenesis and surgical complications

3 months

Long-term Follow-up

Participants are monitored for cancer recurrence

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Spermatogonial Stem Cell Transplant and Testicular Tissue Grafting

Trial Overview The study tests the safety and feasibility of restoring fertility through spermatogonial stem cell transplant and testicular tissue grafting in participants who've had gonadotoxic therapy.

How Is the Trial Designed?

Group I: Spermatogonial Stem Cell Transplant & Testicular Tissue Graft Experimental Treatment 1 Intervention

Stem cell transplantation Testicular tissue grafting

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Published Research Related to This Trial

Spermatogonial stem cell (SSC) transplantation can effectively restore spermatogenesis in a mouse model of B cell acute lymphocytic leukemia, with significant proliferation of SSCs observed after 12 weeks.

Using immunomagnetic beads and flow cytometry for SSC purification was shown to be safe, as it did not lead to tumor cell infiltration in recipient mice, unlike the density gradient centrifugation method, suggesting a safer approach for fertility preservation in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative safety of various spermatogenic stem cell purification methods for application in spermatogenic stem cell transplantation. Tian, J., Ma, K., Pei, CB., et al.[2020]

The study successfully isolated and characterized spermatogonial stem cells (SSCs) from testicular tissue, demonstrating distinct expression levels of key genes during their differentiation process, which is crucial for understanding their role in fertility.

Transplantation of SSCs into busulfan-treated mice resulted in the development of GFP-labeled sperm cells, indicating the potential of this technique for future infertility treatments and in vivo studies of SSC differentiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful transplantation of spermatogonial stem cells into the seminiferous tubules of busulfan-treated mice. Azizi, H., Niazi Tabar, A., Skutella, T.[2021]

Cancer treatments can harm spermatogonial stem cells (SSCs), leading to a risk of infertility in young boys, which highlights the importance of fertility preservation methods.

Recent approaches, such as freezing and reimplanting testicular tissue, are being explored to restore sperm production, with ongoing studies in animal models focusing on techniques like in vivo transplantation of SSCs and testicular grafting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cryopreservation of testicular tissue in children]. Rives, N., Milazzo, JP., Travers, A., et al.[2014]

In this study involving human spermatogonial stem cells (SSCs) transplanted into azoospermic mouse testes, both in vitro transplantation (IVT) and in vivo methods resulted in a significant increase in the number of SSCs and their successful integration into the seminiferous tubules compared to control groups after two weeks.

The expression of the PLZF protein confirmed the identity of the transplanted SSCs, and while both transplantation methods showed similar gene expression levels, the study highlights the potential of testicular tissue culture conditions to enhance SSC integration into the testis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Human Spermatogonial Stem Cells Homing in Recipient Mouse Testis after In Vitro Transplantation and Organ Culture. Mohaqiq, M., Movahedin, M., Mazaheri, Z., et al.[2022]

Human spermatogonial stem cells (SSCs) can be successfully propagated in vitro for up to 6 weeks, indicating their potential for applications in germ cell transplantation and fertility preservation.

The study identified specific markers, Oct4 and PLZF, that are crucial for confirming the presence and viability of human germ stem cells (hGSCs) during culture, highlighting the effectiveness of the growth factors used in the culture media.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propagation of human germ stem cells in long-term culture. Akhondi, MM., Mohazzab, A., Jeddi-Tehrani, M., et al.[2021]

Spermatogonial stem cells (SSC) are crucial for sperm production and can be cryopreserved and transplanted to help preserve fertility in young boys at risk of losing these cells due to treatments like chemotherapy.

Two main strategies for fertility restoration are being developed: injecting SSC directly or grafting testicular tissue containing SSC, with grafting being preferred when safe, as it maintains the natural environment for the cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fertility preservation in boys: spermatogonial stem cell transplantation and testicular grafting]. Goossens, E., Tournaye, H.[2013]

The study demonstrated that injecting mouse spermatogonial stem cells into human cadaver testes is feasible, with GFP-positive cells successfully observed in the seminiferous tubules after ultrasound-guided injection.

Different injection volumes and concentrations affected the distribution of the cells, with the highest concentration showing a significant presence in the testes, indicating potential for optimizing SSC transplantation for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testicular cell transplantation into the human testes. Faes, K., Tournaye, H., Goethals, L., et al.[2015]

Spermatogonial stem cell (SSC) culture and transplantation can potentially restore fertility in male prepubertal cancer survivors, providing a critical pathway for future clinical applications.

The methods for isolating, freezing, and transplanting SSCs have been successfully demonstrated in mice, indicating their potential for translation into human clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation, Cryopreservation, and Transplantation of Spermatogonial Stem Cells. Sinha, N., Whelan, EC., Brinster, RL.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04452305

Spermatogonial Stem Cell (SSC) Transplant and Testicular ... The first approach is autologous transplantation of testicular cells, including spermatogonial stem cells, into the testis using ultrasound-guided rete testis ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3580057/

Spermatogonial stem cell transplantation into Rhesus testes ... Our results indicate that transplanted SSCs can regenerate spermatogenesis in busulfan-treated primates and produce functional sperm capable of fertilizing ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2090598X17301493

Spermatogonial stem cell transplantation and male infertility Grafting spermatogonial stem cells by autotransplantation may be a beneficial infertility treatment in younger males who are to undergo fertility-ablative ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04452305/spermatogonial-stem-cell-ssc-transplant-and-testicular-tissue-grafting

Spermatogonial Stem Cell (SSC) Transplant and Testicular ... This study will test the safety and feasibility of two approaches to restore sperm production using previously cryopreserved testicular tissues.

5. withpower.com withpower.com/trial/phase-infertility-9-2021-2fe0f

SSC Transplant + Testicular Tissue Grafting for Male Infertility Research shows that spermatogonial stem cell (SSC) transplantation and testicular tissue grafting have been successful in animal models, like mice, and are ...

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

Male fertility restoration with stem cell–based therapies This review examines emerging stem cell-based therapies, including testicular tissue grafting, organ culture, cell reconstitution, spermatogonial stem cell ...