An EPO-loaded multifunctional hydrogel synergizing with adipose-derived stem cells restores neurogenic erectile function via enhancing nerve regeneration and penile rehabilitation.
Jun ShaoPan NieWende YangRui GuoDongbing DingRongpu LiangBo WeiHongbo WeiPublished in: Bioengineering & translational medicine (2022)
Neurogenic erectile dysfunction (nED) is one of the most common and intractable postoperative complications of rectal and prostate cancer surgery and sometimes accompanies patients lifelong. The transplantation of stem cells has been proved a promising way for treatment. However, the therapeutic efficacy is severely impaired by excessive cell loss and death and poor accumulation in the injury site along with the traditional implantation strategy. Herein, an EPO-loaded multifunctional hydrogel was designed. The hydrogels' adhesive property and mechanical strength were enhanced by adding catechol-catechol adducts, thus significantly improving adipose-derived stem cells (ADSC) retention and rescuing cell loss in the injury site. Meanwhile, the sustained release of EPO effectively ameliorated the viability and paracrine activity of ADSC, leading to enhanced migration of Schwann cells and differentiation of PC12 cells in vivo. On a bilateral cavernous nerve injury rat model, the present stem cell-EPO-hydrogel implanted strategy could significantly alleviate erectile dysfunction. The higher expression of Tuj1 and lower expression of GFAP in the major pelvic ganglia (MPG) indicated the acceleration of neural differentiation while the suppressing development of astrocytes. Also, the combined therapy restored the expression levels of eNOs, nNOs, and α-SMA in penile tissues, suggesting the rehabilitation of the penis. Further analysis of Masson trichrome staining and apoptosis evaluation of the corpus cavernosum showed the preservation of vascular endothelium content and the prevention of penile fibrosis after denervation. Overall, we believe that this combined strategy presents a promising way not only for restoring neurogenic erectile function but also for the clinical translation of stem cell therapy.
Keyphrases
- cell therapy
- stem cells
- drug delivery
- wound healing
- poor prognosis
- prostate cancer
- cancer therapy
- spinal cord injury
- cell cycle arrest
- radical prostatectomy
- hyaluronic acid
- mesenchymal stem cells
- drug release
- tissue engineering
- cell death
- binding protein
- peripheral nerve
- single cell
- induced apoptosis
- endothelial cells
- ejection fraction
- signaling pathway
- case report
- nitric oxide synthase
- rectal cancer
- newly diagnosed
- long non coding rna
- gene expression
- physical activity
- bone marrow
- coronary artery bypass
- coronary artery disease
- percutaneous coronary intervention