Geng Panpan, Zhang Yuning, Zhang Huan, Dong Xiwen, Yang Yuefeng, Zhu XiaoNa, Wu Chu-Tse, Wang Hua
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
The Fifth Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China.
Stem Cells Int. 2021 Mar 2;2021:6662831. doi: 10.1155/2021/6662831. eCollection 2021.
Paraquat (PQ) poisoning can cause acute lung injury and progress to pulmonary fibrosis and eventually death without effective therapy. Mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) have been shown to partially reverse this damage. MSCs can be derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), umbilical cord (UC-MSCs), dental pulp (DPSCs), and other sources. The biological characteristics of MSCs are specific to the tissue source. To develop an effective treatment for PQ poisoning, we compared the anti-inflammatory and antifibrotic effects of UC-MSCs and DPSCs and chose and modified a suitable source with HGF to investigate their therapeutic effects in vitro and in vivo. In this study, MSCs' supernatant was beneficial to the viability and proliferation of human lung epithelial cell BEAS-2B. Inflammatory and fibrosis-related cytokines were analyzed by real-time PCR. The results showed that MSCs' supernatant could suppress the expression of proinflammatory and profibrotic cytokines and increase the expression of anti-inflammatory and antifibrotic cytokines in BEAS-2B cells and human pulmonary fibroblast MRC-5. Extracellular vesicles (EVs) derived from MSCs performed more effectively than MSCs' supernatant. The effect of DPSCs was stronger than that of UC-MSCs and was further strengthened by HGF modification. PQ-poisoned mice were established, and UC-MSCs, DPSCs, and DPSCs-HGF were administered. Histopathological assessments revealed that DPSCs-HGF mitigated lung inflammation and collagen accumulation more effectively than the other treatments. DPSCs-HGF reduced lung permeability and increased the survival rate of PQ mice from 20% to 50%. Taken together, these results indicated that DPSCs can suppress inflammation and fibrosis in human lung cells better than UC-MSCs. The anti-inflammatory and antifibrotic effects were significantly enhanced by HGF modification. DPSCs-HGF ameliorated pulmonitis and pulmonary fibrosis in PQ mice, effectively improving the survival rate, which might be mediated by paracrine mechanisms. The results suggested that DPSCs-HGF transplantation was a potential therapeutic approach for PQ poisoning.
百草枯（PQ）中毒可导致急性肺损伤，若不进行有效治疗，会进展为肺纤维化并最终导致死亡。间充质干细胞（MSCs）和肝细胞生长因子（HGF）已被证明可部分逆转这种损伤。MSCs可来源于骨髓（BM - MSCs）、脂肪组织（AD - MSCs）、脐带（UC - MSCs）、牙髓（DPSCs）及其他来源。MSCs的生物学特性因组织来源而异。为开发一种有效的PQ中毒治疗方法，我们比较了UC - MSCs和DPSCs的抗炎和抗纤维化作用，并选择并修饰了一种合适的来源与HGF联合，以研究它们在体外和体内的治疗效果。在本研究中，MSCs的上清液有利于人肺上皮细胞BEAS - 2B的活力和增殖。通过实时PCR分析炎症和纤维化相关细胞因子。结果表明，MSCs的上清液可抑制BEAS - 2B细胞和人肺成纤维细胞MRC - 5中促炎和促纤维化细胞因子的表达，并增加抗炎和抗纤维化细胞因子的表达。源自MSCs的细胞外囊泡（EVs）比MSCs的上清液表现更有效。DPSCs的效果强于UC - MSCs，且通过HGF修饰进一步增强。建立了PQ中毒小鼠模型，并给予UC - MSCs、DPSCs和DPSCs - HGF。组织病理学评估显示，DPSCs - HGF比其他治疗更有效地减轻了肺部炎症和胶原积累。DPSCs - HGF降低了肺通透性，并将PQ小鼠的存活率从20%提高到50%。综上所述，这些结果表明，DPSCs比UC - MSCs能更好地抑制人肺细胞中的炎症和纤维化。HGF修饰显著增强了抗炎和抗纤维化作用。DPSCs - HGF改善了PQ小鼠的肺炎和肺纤维化，有效提高了存活率，这可能是通过旁分泌机制介导的。结果表明，DPSCs - HGF移植是一种治疗PQ中毒的潜在方法。
