Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production

Area of Science:

• Reproductive Biology
• Stem Cell Therapy
• Endocrinology

Background:

• Rodent stem Leydig cell (SLC) transplantation shows promise for treating hypogonadism by restoring testosterone production.
• Human SLCs have not been prospectively isolated or evaluated for therapeutic potential in hypogonadism.
• Leydig cells (LCs) are crucial for testosterone synthesis, and their disruption leads to hypogonadism.

Purpose of the Study:

• To prospectively isolate human SLCs and assess their therapeutic potential for hypogonadism.
• To investigate the characteristics and differentiation capacity of isolated human SLCs.
• To evaluate the efficacy of human SLC transplantation in restoring testosterone production in a preclinical model.

Main Methods:

• Human adult testes were used to isolate p75 neurotrophin receptor positive (p75+) cells via flow cytometry.
• In vitro expansion, self-renewal, and multi-lineage differentiation potential of p75+ cells were assessed.
• p75+ cells were transplanted into ethane dimethane sulfonate (EDS)-treated rat models with Leydig cell disruption.

Main Results:

• Isolated p75+ cells expressed SLC markers (nestin) but not LC markers (HSD3β).
• p75+ cells demonstrated in vitro self-renewal and differentiation into testosterone-producing LCs.
• Transplanted p75+ cells differentiated into LCs in vivo, restored physiological testosterone secretion, and improved spermatogenesis and organ weights in EDS-treated rats.

Conclusions:

• A method for identifying and isolating human SLCs based on p75 expression was established.
• Transplanted human p75+ SLCs can differentiate into functional LCs and restore testosterone production in vivo.
• These findings support the clinical application of human SLC transplantation for treating hypogonadism.