Extracellular Vesicles Protect the Neonatal Lung from Hyperoxic Injury Through the Epigenetic and Transcriptomic Reprogramming of Myeloid Cells


Posted: 2021-10-26 19:00:00
Rationale: Mesenchymal stem/stromal cell (MSC)-small extracellular vesicle (MEx) treatment has shown promise in models of neonatal lung injury. The molecular mechanisms by which MEx afford beneficial effects remain incompletely understood. Objective: To investigate the therapeutic mechanism of action through assessment of MEx biodistribution and impact on immune cell phenotypic heterogeneity. Methods: MEx were isolated from the conditioned medium of human umbilical cord Wharton's Jelly-derived MSCs. Newborn mice were exposed to hyperoxia (HYRX, 75% O2) from birth and returned to room air at postnatal day (PN) 14. Mice received either a bolus intravenous MEx dose at PN4 or bone marrow-derived myeloid cells (BMDMy) pretreated with MEx. Animals were harvested at PN4, 7, 14, or 28 to characterize MEx biodistribution or for assessment of pulmonary parameters. The therapeutic role of MEx-educated BMDMy was determined in vitro and in vivo. Measurements and results: MEx therapy ameliorated core histological features of HYRX-induced neonatal lung injury. Biodistribution and mass cytometry studies demonstrated that MEx localize in the lung and interact with myeloid cells. MEx restored the apportion of alveolar macrophages in the HYRX injured lung and concomitantly suppressed inflammatory cytokine production. In vitro and ex vivo studies revealed that MEx promoted an immunosuppressive BMDMy phenotype. Functional assays demonstrated that the immunosuppressive actions of BMDMy are driven by phenotypically and epigenetically reprogrammed monocytes. Adoptive transfer of MEx-educated BMDMy, but not naïve BMDMy, restored alveolar architecture, blunted fibrosis and pulmonary vascular remodeling and improved exercise capacity. Conclusion: MEx ameliorates hyperoxia-induced neonatal lung injury though epigenetic and phenotypic reprogramming of myeloid cells. Keywords: Bronchopulmonary dysplasia; Exosome; Hyperoxia; Lung injury; Neonate.

参考サイト PubMed: exsome



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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