Antenatal Mesenchymal Stromal Cell Extracellular Vesicle Therapy Prevents Preeclamptic Lung Injury in Mice


Posted: 2021-10-06 19:00:00
Am J Respir Cell Mol Biol . 2021 Oct 6. doi: 10.1165/rcmb.2021-0307OC. Online ahead of print. Affiliations Expand Affiliations 1 Harvard Medical School, 1811, Boston Children's Hospital, Boston, Massachusetts, United States. 2 Children's Hospital, Boston, Newborn Medicine, Boston, Massachusetts, United States. 3 Children's Hospital Boston, 1862, Boston, Massachusetts, United States. 4 Boston Children's Hospital, Department of Medicine, Division of Newborn Medicine, Boston, Massachusetts, United States. 5 Harvard Medical School, 1811, Department of Pediatrics, Boston, Massachusetts, United States. 6 Harvard Medical School, 1811, Boston, Massachusetts, United States. 7 Boston Children's Hospital, Division of Newborn Medicine, Boston, Massachusetts, United States. 8 Stanford University School of Medicine, 10624, Pediatrics, Stanford, California, United States. 9 Lucile Salter Packard Children's Hospital at Stanford, 24349, Palo Alto, California, United States. 10 Boston Children's Hospital, 1862, Pediatrics, Boston, Massachusetts, United States. 11 Harvard Medical School, 1811, Pediatics, Boston, Massachusetts, United States. 12 Harvard Medical School, 1811, Boston Children's Hospital, Boston, Massachusetts, United States; stella.kourembanas@childrens.harvard.edu. Item in Clipboard Elizabeth S Taglauer et al. Am J Respir Cell Mol Biol. 2021. Show details Display options Display options Format Am J Respir Cell Mol Biol . 2021 Oct 6. doi: 10.1165/rcmb.2021-0307OC. Online ahead of print. Affiliations 1 Harvard Medical School, 1811, Boston Children's Hospital, Boston, Massachusetts, United States. 2 Children's Hospital, Boston, Newborn Medicine, Boston, Massachusetts, United States. 3 Children's Hospital Boston, 1862, Boston, Massachusetts, United States. 4 Boston Children's Hospital, Department of Medicine, Division of Newborn Medicine, Boston, Massachusetts, United States. 5 Harvard Medical School, 1811, Department of Pediatrics, Boston, Massachusetts, United States. 6 Harvard Medical School, 1811, Boston, Massachusetts, United States. 7 Boston Children's Hospital, Division of Newborn Medicine, Boston, Massachusetts, United States. 8 Stanford University School of Medicine, 10624, Pediatrics, Stanford, California, United States. 9 Lucile Salter Packard Children's Hospital at Stanford, 24349, Palo Alto, California, United States. 10 Boston Children's Hospital, 1862, Pediatrics, Boston, Massachusetts, United States. 11 Harvard Medical School, 1811, Pediatics, Boston, Massachusetts, United States. 12 Harvard Medical School, 1811, Boston Children's Hospital, Boston, Massachusetts, United States; stella.kourembanas@childrens.harvard.edu. Item in Clipboard CiteDisplay options Display options Format Abstract In preeclamptic pregnancies, a variety of intrauterine alterations lead to abnormal placentation, release of inflammatory/antiangiogenic factors, and subsequent fetal growth restriction with significant potential to cause a primary insult to the developing fetal lung. Thus, modulation of the maternal intrauterine environment may be a key therapeutic avenue to prevent preeclampsia-associated developmental lung injury. A biologic therapy of interest are mesenchymal stromal cell-derived extracellular vesicles (MEx), which we have previously shown to ameliorate preeclamptic physiology through intrauterine immunomodulation. To evaluate the therapeutic potential of MEx to improve developmental lung injury in experimental preeclampsia. Using the heme oxygenase-1 null mouse (Hmox1-/-) model, preeclamptic pregnant dams were administered intravenous antenatal MEx treatment during each week of pregnancy followed by analysis of fetal and postnatal lung tissues, amniotic fluid protein profiles and lung explant/amniotic fluid co-cultures in comparison with control and untreated preeclamptic pregnancies. We first identified that a preeclamptic intrauterine environment had a significant adverse impact on fetal lung development including alterations in fetal lung developmental gene profiles in addition to postnatal alveolar and bronchial changes. Amniotic fluid proteomic analysis and fetal lung explant/amniotic fluid co-cultures further demonstrated that maternally administered MEx altered the expression of multiple inflammatory mediators in the preeclamptic intrauterine compartment resulting in normalization of fetal lung branching morphogenesis and developmental gene expression. Our evaluation of fetal and postnatal parameters overall suggests that antenatal MEx treatment may provide a highly valuable preventative therapeutic modality for amelioration of lung development in preeclamptic disease. Keywords: Lung development, preeclampsia, exosomes, bronchopulmonary dysplasia.

参考サイト PubMed: exsome


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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
9月 27, 2021 バイオアソシエイツ

天然の機能を持つ合成エクソソームを開発。創傷治癒や新しい血管の形成を制御・支援する重要なメカニズムが明らかに。

マックスプランク医学研究所(ドイツ・ハイデルベルグ)とDWIライプニッツ相互作用材料研究所(ドイツ・アーヘン)の研究者らは、創傷閉鎖時の細胞シグナルを制御する合成エクソソームを開発した。この合成構造は、体内のさまざまなプロセスで細胞間のコミュニケーションに基本的な役割を果たしている、天然の細胞外小胞[編集部注:エクソソームは細胞外小胞のサブセット]に似せて作られている。この研究者は、創傷治癒や新しい血管の形成を制御・支援する重要なメカニズムを明らかにした。細胞から天然の細胞外小胞を分離するのではなく、プログラム可能…

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