Stem cells treatment for NOA

Treatment of non-obstructive azoospermia (NOA) using stem cells is a promising area in reproductive medicine. Recent clinical studies demonstrate the potential of this therapy in restoring spermatogenesis in men with NOA.

READ MORE ABOUT : NEW PROTOCOL OF AZOOSPERMIA TREATMENT

The most common protocols for using stem cells in the treatment of azoospermia.

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Bone marrow mesenchymal stem cells (MSCs)
One clinical study showed that autologous MSC transplantation into the seminiferous tubules contributed to the regeneration of the seminiferous tubules and normalization of the hormonal profile regulating spermatogenesis. This confirms the safety and efficacy of autologous MSCs as a promising method for treating NOA, especially in patients with secondary infertility.
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Spermatogonial stem cell (SSC) transplantation
In 2024, the world’s first SSC transplantation protocol was performed in a 26-year-old man who lost fertility after chemotherapy in childhood. The patient’s own SSCs, frozen before treatment, were reintroduced into his testicles. Although no sperm have been detected yet, hormone levels and tissue structure remain normal. The researchers hope that this will eventually lead to the production of sperm suitable for IVF.
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Combination approaches: NOA-SERA
The NOA-SERA protocol combines autologous mobilized progenitor cells and platelet-derived growth factors to restore spermatogenesis in patients with NOA. Preliminary results show improvement in testicular function, but more research is needed to confirm the effectiveness of this approach. ________________________________________

Success of our protocol for the treatment of non-obstructive azoospermia (cause of disease is not established)

It is important to create a microenvironment (niche) in the treatment of this form of azoospermia, which supports the differentiation of spermatogonia
Mechanism:
• MSCs secrete growth factors (GDNF, SCF, IGF1), which regulate spermatogenesis
• Reduce local inflammation and fibrosis
• Restore the activity of Sertoli cells

Personalized therapy with growth factors from stem cells (cocktail complex):

It can be used both locally and intravenously with controlled release of GDNF, BMP4, FGF2 – this promotes the advancement of spermatocytes to the spermatid stage.

Implantation of induced spermatogenic niches in vitro (with subsequent suturing into adipose tissue)

To enhance the result, we can consider seminiferous tubule organoids grown with the participation of MSCs and Sertoli cells, with subsequent autologous transplantation.      Azoospermia Treatment with Stem Cells: Patient Case Study

The success of our protocol for the treatment of non-obstructive azoospermia (reason: dominance of female sex hormones over androgens.)

The exact causes are usually not visible in tests and diagnostics, but there is a violation of sperm maturation, disturbances in biochemical processes in cells, disruption of the hypothalamic axis (nerve connections with the reproductive system), organic stimulation of the FSH hormone and sensitive distribution of androgens, damage to the function of AP cells AP/B cells, which give regression. This can be either one factor or a combination of them.
The treatment principle may remain with the basic mechanism of creating a microenvironment (niche) that supports spermatogonial differentiation + implantation of NR3C4 (Androgen receptor, AR) receptor cells plays a critical role in prostate epithelial homeostasis, neurovascular integrity and sexual function. Dysregulation of AR expression or activity contributes to chronic prostatitis, androgen deficiency syndromes, erectile dysfunction (ED) and benign prostatic hyperplasia (BPH). Exosome-based AR delivery. MSC exosomes carrying AR-modulating miRNA or mRNA can regulate androgen signaling in erectile dysfunction.

The success of our protocol for the treatment of non-obstructive azoospermia (reason: vascular disorders, testicular atrophy, glandular hyperplasia)

The basis of the protocol does not change, only a narrow part of cell cultures is supplemented, which will affect the creation of new vascular branches (angiogenesis), improve blood circulation, restore nutrition of trophic tissues. Most often, endothelial progenitor stem cells are used in combination with growth factors and mitochondrial cells to improve cellular “communication and exchange”.
Implantation of induced spermatogenic niches in vitro is a promising and high-tech method that is being developed for the treatment of non-obstructive azoospermia (NOA), especially in cases where there are no spermatozoa in the testicles.
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Let’s look into the new protocols and new techniques that we are already actively using.

What is implantation of induced spermatogenic niches in vitro?

The spermatogenic niche is the microenvironment inside the testicle where all stages of sperm formation occur.

It includes:
• Sertoli cells (nutrition and support of spermatogonia),
• Leydig cells (hormonal regulation),
• basement membrane and stem cells (spermatogonia).
In vitro induction is the creation of such a microenvironment in the laboratory using biocompatible materials and cells from the patient or donor.
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How it works in practice:
1. Stem cells (mesenchymal or induced pluripotent iPSCs) are extracted from the patient.
2. They are reprogrammed into cells close to spermatogonia or auxiliary (Sertoli).
3. A 3D model of testicular tissue is created – this is the induced niche.
4. The niche is implanted into the patient – in a biocompatible capsule (for example, under the skin in adipose tissue), where it can potentially begin producing sperm.
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Potential applications:
• For patients with total azoospermia, where even microTESE does not detect sperm.
• In congenital genetic abnormalities (e.g. AZF deletion on the Y chromosome).
• To restore fertility after chemotherapy or radiotherapy.

Administration of seminiferous tubule organoids grown with MSCs and Sertoli cells, followed by autologous transplantation.

 

Seminiferous tubule organoids are three-dimensional (3D) structures created in the laboratory from testicular cells that mimic the architecture and function of natural seminiferous tubules. They represent an innovative model for studying spermatogenesis and potential treatment of male infertility, including non-obstructive azoospermia (NOA).
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What are seminiferous tubule organoids?
Organoids are formed by culturing testicular cells (e.g. spermatogonial stem cells, Sertoli cells, Leydig cells, etc.) under special conditions that promote their self-organization into structures resembling seminiferous tubules. These 3D models (3D organoids) reproduce the cellular interactions and microenvironment required for normal spermatogenesis.
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Application of organoids in the treatment of azoospermia
In the context of NOA, where traditional methods such as microTESE are not always effective, organoids offer an alternative approach:
• In vitro modeling of spermatogenesis: Organoids allow us to study the differentiation processes of spermatogonial stem cells and identify factors that influence successful sperm formation.
• Personalized medicine: Creating organoids from patient-specific cells can help develop individualized treatment strategies for infertility.
SUCCESS RATE OF AZOOSPERMIA THERAPY
An individual approach to each clinical case makes it possible to accurately determine the cause of azoospermia and select the appropriate treatment protocol.