Matz Ethan L, Thakker Parth U, Gu Xin, Terlecki Ryan P, Dou Lei, Walker Stephen J, Lue Tom, Lin Guiting, Atala Anthony, Yoo James J, Zhang Yuanyuan, Jackson John D
Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
Department of Urology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
J Tissue Eng Regen Med. 2020 Oct;14(10):1394-1402. doi: 10.1002/term.3105. Epub 2020 Jul 31.
Human placental stem cells (PSCs) enhance histological and functional recovery in a rodent erectile dysfunction (ED) model. We tested the hypothesis that bioactive factors secreted by PSC (i.e., the secretome) mediate functional recovery and that acellular-conditioned media (CM) from PSC culture (PSC-CM) could be used independently to facilitate functional and histological recovery. To identify factors relative to efficacy of PSC, a comparison of CM from PSC and three additional human stem cell populations was performed. CM from human PSC, amniotic fluid stem cells (AFSCs), adipose-derived stem cells (ADSC), and human umbilical vein endothelial cells (HUVECs) was assayed using a semi-quantitative human cytokine antibody array. Male rats, after surgically created ED by neurovascular injury, were randomly divided into four groups: vehicle control (phosphate-buffered saline [PBS]), PSC, PSC-CM, and serum-free media control (SFM) as control. Functional data on intracorporal and mean arterial pressure were obtained, and histological architecture was examined 6 weeks after single injection. PSCs were found to secrete at least 27 cytokines and growth factors at a significantly higher level than the other three cell types. Either single injection of PSC-CM or PSC significantly improved erectile functional recovery and histological architecture compared with SFM or PBS. Injection of the secretome isolated from human PSC improves erectile functional recovery and histological structure in a rat model of neurovascular injury-induced ED. Further characterization of the unique protein expression within the PSC-CM may help to identify the potential for a novel injectable cell-free therapeutic for applicable patients.
人胎盘干细胞(PSCs)可促进啮齿动物勃起功能障碍(ED)模型的组织学和功能恢复。我们验证了以下假设:PSC分泌的生物活性因子(即分泌组)介导功能恢复,并且来自PSC培养物的无细胞条件培养基(CM)(PSC-CM)可独立用于促进功能和组织学恢复。为了鉴定与PSC疗效相关的因子,对PSC和另外三种人类干细胞群体的CM进行了比较。使用半定量人细胞因子抗体阵列检测来自人PSC、羊水干细胞(AFSCs)、脂肪来源干细胞(ADSCs)和人脐静脉内皮细胞(HUVECs)的CM。雄性大鼠在通过神经血管损伤手术造成ED后,随机分为四组:载体对照(磷酸盐缓冲盐水[PBS])、PSC、PSC-CM和无血清培养基对照(SFM)作为对照。在单次注射6周后获得体内和平均动脉压的功能数据,并检查组织结构。发现PSC分泌至少27种细胞因子和生长因子,其水平明显高于其他三种细胞类型。与SFM或PBS相比,单次注射PSC-CM或PSC均能显著改善勃起功能恢复和组织结构。注射从人PSC分离的分泌组可改善神经血管损伤诱导的ED大鼠模型的勃起功能恢复和组织结构。进一步表征PSC-CM内独特的蛋白质表达可能有助于确定一种新型可注射无细胞疗法对适用患者的潜力。