From Mesenchymal Stromal Cells to Extracellular Vesicles: Scalable Strategies for Ovarian Stroma Regeneration

Area of Science:

• Reproductive Biology
• Gerontology
• Biotechnology

Background:

• Ovarian aging is marked by reduced follicles and oocyte quality.
• Stromal deterioration, including ECM remodeling and cell signaling dysfunction, is increasingly recognized as a key factor in ovarian aging.
• Current understanding highlights the complex interplay of structural, molecular, and cell communication disruptions within the ovarian stroma.

Purpose of the Study:

• To review the primary shifts in ovarian stroma associated with aging.
• To emphasize the roles of extracellular matrix (ECM) remodeling, biomechanical alterations, and cell signaling dysfunction.
• To explore Mesenchymal Stromal Cells (MSCs) and Extracellular Vesicles (EVs) as therapeutic strategies for ovarian stromal regeneration.

Main Methods:

• Literature review focusing on ovarian aging and stromal changes.
• Analysis of the mechanisms of action for MSCs and EVs in modulating inflammation, ECM, and cell communication.
• Discussion of the transition from cell-based to cell-free therapies using EVs.
• Examination of translational challenges in developing stroma-targeted interventions.

Main Results:

• Stromal deterioration is a central component of ovarian aging, involving ECM remodeling and disrupted cell signaling.
• MSCs and their secreted EVs offer a promising therapeutic avenue due to their regenerative and immunomodulatory properties.
• EVs present advantages over MSCs in safety and manufacturability, facilitating cell-free therapeutic approaches.

Conclusions:

• Ovarian aging is multifactorial, with stromal dysfunction playing a critical role.
• MSCs and EVs hold significant potential for regenerating ovarian stroma and restoring function.
• Addressing translational challenges like scalability and quality control is essential for developing effective ovarian therapies.