Wang Bei-Ying, Zhang Xiao, Li Ting-Tian, Qin Wei-Wei, Liu Xiang, Lu Kong-Miao, Sun Li-Xin, Han Wei
Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, 211166, China.
Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, 266071, China.
Stem Cell Res Ther. 2025 Jul 26;16(1):407. doi: 10.1186/s13287-025-04545-6.
Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating acute respiratory distress syndrome (ARDS), however, their homing to the lungs and survival time are insufficient. In this study, we evaluated whether pulsed focus ultrasound (pFUS) could promote the homing and prolonged retention of hUC-MSCs in the lungs of ARDS mice and explored the mechanisms involved.
Mice were divided into four groups: the NC group, the LPS group, the MSCs group, and the pFUS + MSCs group. Except for the NC group, the other three groups were constructed as ARDS models and given PBS, MSCs and pFUS + MSCs interventions. hUC-MSCs were used to assess lung tissue injury by HE staining, inflammatory cell count in alveolar lavage fluid (BALF), and expression of Tnf, Il1b and Il6 in the lung tissues; and apoptosis and proliferation in the lung tissues were assessed by TUNEL and immunofluorescence. Bioluminescence imaging was used to detect the homing rate and survival of hUC-MSCs in mouse lungs from 1 to 7 days. Cxcl5 and Igf1 was found to be differentially expressed and highly enriched by mRNA sequencing in MSC and sonicated groups and verified by PCR combined with ELISA.
Compared with the LPS group, the lung inflammatory infiltrate and lung tissue damage in the MSCs group and pFUS + MSC group were alleviated, the number of inflammatory cells in the BALF and the expression of Tnf, Il1b and Il6 in the lung tissues were reduced, the expression of TUNEL-positive cells was reduced, and the expression of PCNA-positive cells was increased, and the decrease or increase was more significant in the pFUS + MSC group (P < 0.05). pFUS increased the number of hUC-MSCs homing in the lungs and prolonged lung survival to day 6 and significantly up-regulated lung tissue levels of SDF-1, ICAM-1, CXCL5 and IGF-1 compared to the MSCs group (P < 0.05).
pFUS preconditioning may improve lung homing and prolong survival of hUC-MSCs by upregulating the levels of homing-associated factors SDF-1, ICAM-1, CXCL5 and IGF-1, which in turn improves ARDS.
人脐带间充质干细胞（hUC-MSCs）在治疗急性呼吸窘迫综合征（ARDS）方面显示出潜力，然而，它们归巢至肺部的能力以及存活时间不足。在本研究中，我们评估了脉冲聚焦超声（pFUS）是否能促进hUC-MSCs在ARDS小鼠肺部的归巢和延长其滞留时间，并探讨其中涉及的机制。
将小鼠分为四组：NC组、LPS组、MSCs组和pFUS + MSCs组。除NC组外，其他三组构建为ARDS模型，并分别给予PBS、MSCs和pFUS + MSCs干预。采用hUC-MSCs通过HE染色评估肺组织损伤、肺泡灌洗液（BALF）中的炎性细胞计数以及肺组织中Tnf、Il1b和Il6的表达；通过TUNEL和免疫荧光评估肺组织中的凋亡和增殖情况。利用生物发光成像检测1至7天内hUC-MSCs在小鼠肺部的归巢率和存活率。通过mRNA测序发现Cxcl5和Igf1在MSC组和超声处理组中差异表达且高度富集，并通过PCR结合ELISA进行验证。
与LPS组相比，MSCs组和pFUS + MSC组的肺部炎性浸润和肺组织损伤减轻，BALF中的炎性细胞数量以及肺组织中Tnf、Il1b和Il6的表达降低，TUNEL阳性细胞的表达降低，PCNA阳性细胞的表达增加，且在pFUS + MSC组中这种降低或增加更为显著（P < 0.05）。与MSCs组相比，pFUS增加了hUC-MSCs在肺部的归巢数量，并将肺部存活时间延长至第6天，且显著上调了肺组织中SDF-1、ICAM-1、CXCL5和IGF-1的水平（P < 0.05）。
pFUS预处理可能通过上调归巢相关因子SDF-1, ICAM-1, CXCL5和IGF-1的水平来改善hUC-MSCs的肺归巢并延长其存活时间，进而改善ARDS。
