Yan Hao, Rong Liduo, Xiao Dongdong, Zhang Ming, Sheikh Søren Paludan, Sui Xiaofeng, Lu Mujun
Department of Urology and Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China.
Key Lab of Science and Technology of Eco-textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
Mater Sci Eng C Mater Biol Appl. 2020 Nov;116:111214. doi: 10.1016/j.msec.2020.111214. Epub 2020 Jun 20.
Diabetic erectile dysfunction has witnessed extensive preclinical and clinical explorations of intracavernous injection of stem cells therapy. However, intracavernous injection of stem cells for diabetic erectile dysfunction is challenged by rapid diffusion from cavernous sinus. Here, we found that a benzaldehyde terminated poly (ethylene glycol)/glycol chitosan (CHO-PEG/GCS) hydrogel with injectability and self-healability served as a stem cell carrier to prolong cell retention in corpus cavernosum. It was able to gelate under physiological condition and encapsulate adipose stem cells (ASCs) without reducing proliferation after injection. Encapsulated labelled ASCs presented higher fluorescence than non-encapsulated ones in the region of penis at 14 days after intracavernous injection in male rats. CHO-PEG/GCS hydrogel enhanced ASCs to ameliorate diabetes-induced fibrosis and apoptosis of CD31-positive endothelial cells, α-SMA-positive smooth muscle and NeuN-positive neural fibers 12 weeks post-operation. It also synergized with ASCs to elevate cGMP level and promote erectile function. CHO-PEG/GCS hydrogel serves as a promising stem cell carrier in conditions requiring injection and in situ gelation to prolong cell retention.
糖尿病性勃起功能障碍已经经历了对海绵体内注射干细胞疗法的广泛临床前和临床探索。然而，用于糖尿病性勃起功能障碍的海绵体内注射干细胞受到从海绵窦快速扩散的挑战。在此，我们发现一种具有可注射性和自愈性的苯甲醛封端的聚乙二醇/乙二醇壳聚糖（CHO-PEG/GCS）水凝胶可作为干细胞载体，以延长细胞在海绵体中的保留时间。它能够在生理条件下凝胶化并封装脂肪干细胞（ASC），注射后不会降低其增殖能力。在雄性大鼠海绵体内注射14天后，封装标记的ASC在阴茎区域的荧光高于未封装的ASC。CHO-PEG/GCS水凝胶增强了ASC改善糖尿病诱导的纤维化以及CD31阳性内皮细胞、α-SMA阳性平滑肌和NeuN阳性神经纤维凋亡的能力，术后12周效果显著。它还与ASC协同作用以提高cGMP水平并促进勃起功能。在需要注射和原位凝胶化以延长细胞保留时间的情况下，CHO-PEG/GCS水凝胶是一种有前景的干细胞载体。
