PMID- 35795773 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2022 DP - 2022 TI - Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Type II Cell Proliferation and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia. PG - 8465294 LID - 10.1155/2022/8465294 [doi] LID - 8465294 AB - Although it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide- (LPS-) induced BPD rat model and to clarify the underlying mechanism. We demonstrate that antenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature, which restored by hUCMSCs and MVs treatment. Furthermore, MVs were large vesicles with a diameter of 100-900 nanometers and mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, PTEN/AKT and MAPK pathways were associated with the protection of MVs. Taken together, this study suggests MVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuating lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment. CI - Copyright (c) 2022 Ou Zhou et al. FAU - Zhou, Ou AU - Zhou O AUID- ORCID: 0000-0001-8868-4651 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - You, Jingyi AU - You J AUID- ORCID: 0000-0003-1694-4017 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Xu, Xiaochuan AU - Xu X AUID- ORCID: 0000-0003-1140-7001 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Liu, Jiang AU - Liu J AUID- ORCID: 0000-0002-4418-0416 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Qiu, Huijun AU - Qiu H AUID- ORCID: 0000-0002-6974-648X AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Hao, Chang AU - Hao C AUID- ORCID: 0000-0001-6243-2050 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Zou, Wenjing AU - Zou W AUID- ORCID: 0000-0002-0678-3443 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Wu, Wenjie AU - Wu W AUID- ORCID: 0000-0001-7408-4401 AD - Department of Pediatrics, Chongqing Youyoubaobei Women and Children's Hospital, Chongqing 401122, China. FAU - Fu, Zhou AU - Fu Z AUID- ORCID: 0000-0001-9024-3222 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Tian, Daiyin AU - Tian D AUID- ORCID: 0000-0002-6505-6027 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. FAU - Zou, Lin AU - Zou L AUID- ORCID: 0000-0003-1084-3151 AD - Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China. AD - Center of Clinical Molecular Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. AD - Clinical Research Unit, Children's Hospital of Shanghai Jiaotong University, Shanghai 200062, China. LA - eng PT - Journal Article DEP - 20220627 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC9252687 COIS- The authors declare that they have no competing interests. EDAT- 2022/07/08 06:00 MHDA- 2022/07/08 06:01 PMCR- 2022/06/27 CRDT- 2022/07/07 02:36 PHST- 2022/01/12 00:00 [received] PHST- 2022/06/06 00:00 [revised] PHST- 2022/06/09 00:00 [accepted] PHST- 2022/07/07 02:36 [entrez] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/07/08 06:01 [medline] PHST- 2022/06/27 00:00 [pmc-release] AID - 10.1155/2022/8465294 [doi] PST - epublish SO - Stem Cells Int. 2022 Jun 27;2022:8465294. doi: 10.1155/2022/8465294. eCollection 2022.