Coronado Ramon E, Stavenschi Toth Elena, Somaraki-Cormier Maria, Krishnegowda Naveen, Dallo Shatha
Signature Biologics, 4040 W Royal Lane, Suite 100, Irving, TX 75063, USA.
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
Biomedicines. 2023 Jan 31;11(2):415. doi: 10.3390/biomedicines11020415.
Allogeneic transplant rejection represents a medical complication that leads to high morbidity and mortality rates. There are no treatments to effectively prevent fibrosis; however, there is great interest in evaluating the use of perinatal mesenchymal stromal cells (MSCs) and other MSCs to prevent fibrosis associated with chronic rejection. In this study, we isolated human perinatal stromal cells (PSCs) from amnion (AM-PSC), placental villi (PV-PSC), and umbilical cord (UC-PSC) tissues, demonstrating the phenotypic characteristics of MSCs as well as a >70% expression of the immunomodulatory markers CD273 and CD210. The administration of a single dose (250,000 cells) of each type of PSC in a humanized graft versus host disease (hGvHD) NSG murine model delayed the progression of the disease as displayed by weight loss and GvHD scores ranging at various levels without affecting the hCD3+ population. However, only PV-PSCs demonstrated an increased survival rate of 50% at the end of the study. Furthermore, a histopathological evaluation showed that only PV-PSC cells could reduce human CD45+ cell infiltration and the fibrosis of the lungs and liver. These findings indicate that not all PSCs have similar therapeutic potential, and that PV-PSC as a cell therapeutic may have an advantage for targeting fibrosis related to allograft rejection.
同种异体移植排斥反应是一种会导致高发病率和死亡率的医学并发症。目前尚无有效预防纤维化的治疗方法；然而，人们对评估围产期间充质基质细胞（MSC）及其他MSC用于预防与慢性排斥相关的纤维化有着浓厚兴趣。在本研究中，我们从羊膜（AM-PSC）、胎盘绒毛（PV-PSC）和脐带（UC-PSC）组织中分离出人类围产期基质细胞（PSC），证实了其具有MSC的表型特征以及免疫调节标志物CD273和CD210的表达率>70%。在人源化移植物抗宿主病（hGvHD）NSG小鼠模型中，对每种类型的PSC给予单剂量（250,000个细胞），可延缓疾病进展，表现为体重减轻和不同水平的GvHD评分，且不影响hCD3+细胞群体。然而，只有PV-PSC在研究结束时显示存活率提高了50%。此外，组织病理学评估表明，只有PV-PSC细胞可减少人CD45+细胞浸润以及肺和肝的纤维化。这些发现表明，并非所有PSC都具有相似的治疗潜力，且PV-PSC作为一种细胞疗法在针对同种异体移植排斥相关纤维化方面可能具有优势。
