Evaluation of the efficacy of conditioned medium derived from quality- and quantity-cultured peripheral blood mononuclear cells for erectile dysfunction
TL;DR
Serum-free ex vivo quality- and quantity-cultured peripheral blood mononuclear cells (MNC-QQ), which can be manufactured within 1 week from a minimal volume of peripheral blood, demonstrate therapeutic efficacy in ED through multiple mechanisms, including angiogenesis, promotion of CCSMCs proliferation, and anti-fibrotic activity.
Abstract
Introduction Neurogenic erectile dysfunction (ED) due to cavernous nerve injury (CNI) leads to irreversible apoptosis of the cavernosal smooth muscle and fibrosis. These structural changes are often refractory to conventional treatments. Serum-free ex vivo quality- and quantity-cultured peripheral blood mononuclear cells (MNC-QQ), which can be manufactured within 1 week from a minimal volume of peripheral blood, were developed. MNC-QQ cells are anti-inflammatory, proangiogenic, and antifibrotic, with confirmed efficacy and safety in clinical trials for refractory limb ulcers. Conditioned medium derived from MNC-QQ cells (MNCQQ-CM) contains bioactive factors with anti-inflammatory, angiogenic, and antifibrotic properties. As a cell-free, minimally invasive therapy, it represents a promising regenerative approach. In this study, we aimed to evaluate whether MNCQQ-CM promotes cavernous tissue regeneration in a CNI-induced ED model. Methods Corpus cavernosum smooth muscle cells (CCSMCs) isolated from murine penile tissue were assessed for proliferation and resistance to apoptosis following MNCQQ-CM treatment. Angiogenic capacity was evaluated through proliferation and tube formation assays using human umbilical vein endothelial cells (HUVECs). MNCQQ-CM composition was analyzed using enzyme-linked immunosorbent assay (ELISA). Bilateral CNI was induced in male rats, followed by intracavernosal injection of MNCQQ-CM, and subsequent evaluation of erectile function and histology. Results MNCQQ-CM significantly enhanced CCSMCs proliferation. Under oxidative stress, it reduced CCSMCs apoptosis. Moreover, MNCQQ-CM promoted HUVEC proliferation and tube formation, demonstrating its angiogenic potential. The presence of vascular endothelial growth factor and interleukin-10 in MNCQQ-CM was confirmed by ELISA. In CNI rats, MNCQQ-CM significantly improved erectile function and increased the smooth muscle/collagen ratio. Conclusions MNCQQ-CM demonstrates therapeutic efficacy in ED through multiple mechanisms, including angiogenesis, promotion of CCSMCs proliferation, and anti-fibrotic activity. The synergistic interaction of cytokines in MNCQQ-CM contributes to ED improvement. Given its rapid and minimally invasive production process, MNCQQ-CM holds substantial promise as a novel therapeutic agent for neurogenic diseases.