Mesenchymal stromal cell-derived small extracellular vesicles restore lung architecture and improve exercise capacity in a model of neonatal hyperoxia-induced lung injury

References

• Stenmark KR, Abman SH. Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol. 2005;67:623–14. Epub 2005/ 02/16.
   PubMed Web of Science ®Google Scholar
• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723–1729. Epub 2001/ 06/13.
   PubMedGoogle Scholar
• Mitsialis SA, Kourembanas S. Stem cell-based therapies for the newborn lung and brain: possibilities and challenges. Semin Perinatol. 2016;40(3):138–151. Epub 2016/ 01/19.
   Web of Science ®Google Scholar
• Khemani E, McElhinney DB, Rhein L, et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007;120(6):1260–1269. Epub 2007/ 12/07.
   PubMed Web of Science ®Google Scholar
• Del Cerro MJ, Sabate Rotes A, Carton A, et al. Pulmonary hypertension in bronchopulmonary dysplasia: clinical findings, cardiovascular anomalies and outcomes. Pediatr Pulmonol. 2014;49(1):49–59. Epub 2013/ 06/22.
   Web of Science ®Google Scholar
• Abman SH, Hansmann G, Archer SL, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132(21):2037–2099. Epub 2015/ 11/05.
   PubMed Web of Science ®Google Scholar
• Jain D, Bancalari E. Bronchopulmonary dysplasia: clinical perspective. Birth Defects Res Part A, Clin Mol Teratol. 2014;100(3):134–144. Epub 2014/ 03/01.
   PubMed Web of Science ®Google Scholar
• Stoll BJ, Hansen NI, Bell EF, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. Jama. 2015;314(10):1039–1051. Epub 2015/ 09/09.
   PubMed Web of Science ®Google Scholar
• Matthay MA, Anversa P, Bhattacharya J, et al. Cell therapy for lung diseases. Report from an NIH–NHLBI workshop, November 13–14, 2012. Am J Respir Crit Care Med. 2013;370–375. DOI:10.1164/rccm.201303-0522WS
   Web of Science ®Google Scholar
• Fung ME, Thébaud B. Stem cell-based therapy for neonatal lung disease: it is in the juice. Pediatr Res. 2014;75(1–1):2–7. Epub 2014/ 10/14.
   PubMed Web of Science ®Google Scholar
• Alvarez-Fuente M, Moreno L, Mitchell JA, et al. Preventing bronchopulmonary dysplasia: new tools for an old challenge. Pediatr Res. 2019;85(4):432–441. Epub 2018/ 11/23.
   Web of Science ®Google Scholar
• Kang M, Thebaud B. Stem cell biology and regenerative medicine for neonatal lung diseases. Pediatr Res. 2018;83(1–2):291–297. Epub 2017/ 09/19.
   Web of Science ®Google Scholar
• Willis GR, Mitsialis SA, Kourembanas S. “Good things come in small packages”: application of exosome-based therapeutics in neonatal lung injury. Pediatr Res. 2018;83(1-2):298-307. doi:10.1038/pr.2017.256. Epub 2017/ 10/07.
   Google Scholar
• Aslam M, Baveja R, Liang OD, et al. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 2009;180(11):1122–1130. Epub 2009/ 08/29.
   PubMed Web of Science ®Google Scholar
• Hansmann G, Fernandez-Gonzalez A, Aslam M, et al. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012;2(2):170–181. Epub 2012/ 07/28.
   PubMedGoogle Scholar
• van Haaften T, Byrne R, Bonnet S, et al. Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med. 2009;180(11):1131–1142. Epub 2009/ 08/29.
   PubMed Web of Science ®Google Scholar
• Lee C, Mitsialis SA, Aslam M, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126(22):2601–2611. Epub 2012/ 11/02.
   PubMed Web of Science ®Google Scholar
• Willis GR, Fernandez-Gonzalez A, Anastas J, et al. Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation. Am J Respir Crit Care Med. 2018;197(1):104–116. Epub 2017/ 08/31.
   PubMed Web of Science ®Google Scholar
• Braun RK, Chetty C, Balasubramaniam V, et al. Intraperitoneal injection of MSC-derived exosomes prevent experimental bronchopulmonary dysplasia. Biochem Biophys Res Commun. 2018;503(4):2653–2658. Epub 2018/ 08/11.
   Web of Science ®Google Scholar
• Chaubey S, Thueson S, Ponnalagu D, et al. Early gestational mesenchymal stem cell secretome attenuates experimental bronchopulmonary dysplasia in part via exosome-associated factor TSG-6. Stem Cell Res Ther. 2018;9(1):173.
   PubMed Web of Science ®Google Scholar
• Porzionato A, Zaramella P, Dedja A, et al. Intratracheal administration of clinical-grade mesenchymal stem cell-derived extracellular vesicles reduces lung injury in a rat model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2019;316(1):L6–l19. Epub 2018/ 10/05.
   Web of Science ®Google Scholar
• Morrison TJ, Jackson MV, Cunningham EK, et al. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med. 2017;196(10):1275–1286. Epub 2017/ 06/10.
   PubMed Web of Science ®Google Scholar
• Fujita Y, Kadota T, Araya J, et al. Clinical application of mesenchymal stem cell-derived extracellular vesicle-based therapeutics for inflammatory lung diseases. J Clin Med. 2018;7(10). Epub 2018/ 10/17. DOI:10.3390/jcm7100355.
   Web of Science ®Google Scholar
• Suzuki E, Fujita D, Takahashi M, et al. Therapeutic effects of mesenchymal stem cell-derived exosomes in cardiovascular disease. Adv Exp Med Biol. 2017;998:179–185. Epub 2017/ 09/25.
   PubMed Web of Science ®Google Scholar
• Long Q, Upadhya D, Hattiangady B, et al. Intranasal MSC-derived A1-exosomes ease inflammation and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc Nat Acad Sci. 2017;114(17):E3536–E45.
   Web of Science ®Google Scholar
• Thebaud B, Kourembanas S. Can we cure bronchopulmonary dysplasia? J Pediatr. 2017;191:12–14. Epub 2017/ 09/26.
   Web of Science ®Google Scholar
• Seshareddy K, Troyer D, Weiss ML. Method to isolate mesenchymal-like cells from Wharton’s Jelly of umbilical cord. Methods Cell Biol. 2008;86:101–119. Epub 2008/ 04/30.
   PubMed Web of Science ®Google Scholar
• Thery C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. Epub 2019/ 01/15.
   PubMed Web of Science ®Google Scholar
• Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles. 2019;8(1):1609206. Epub 2019/ 05/10.
   PubMed Web of Science ®Google Scholar
• Mansouri N, Willis GR, Fernandez-Gonzalez A, et al. Mesenchymal stromal cell exosomes prevent and revert experimental pulmonary fibrosis through modulation of monocyte phenotypes. JCI Insight. Epub 2019/ 10/04. 2019;4(21). DOI:10.1172/jci.insight.128060
   PubMed Web of Science ®Google Scholar
• Willis GR, Connolly K, Ladell K, et al. Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles. Hum Reprod. 2014;29(12):2756–2763. Epub 2014/ 10/23.
   Web of Science ®Google Scholar
• Kim DH, Kim HS, Choi CW, et al. Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology. 2012;101(1):40–46. Epub 2011/ 07/28.
   Web of Science ®Google Scholar
• Saugstad OD. Resuscitation of newborn infants: from oxygen to room air. Lancet. 2010;376(9757):1970–1971. Epub 2010/ 07/29.
   Web of Science ®Google Scholar
• Hansen AR, Barnes CM, Folkman J, et al. Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr. 2010;156(4):532–536. Epub 2009/ 12/17.
   PubMed Web of Science ®Google Scholar
• Tang JR, Karumanchi SA, Seedorf G, et al. Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2012;302(1):L36–46. Epub 2011/ 10/18.
   Web of Science ®Google Scholar
• Watterberg KL, Demers LM, Scott SM, et al. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996;97(2):210–215. Epub 1996/ 02/01
   PubMed Web of Science ®Google Scholar
• Hansmann G. Neonatal resuscitation on air: it is time to turn down the oxygen tanks [corrected]. Lancet. 2004;364(9442):1293–1294. Epub 2004/ 10/12.
   Web of Science ®Google Scholar
• Lin H-C, Wang -C-C, Chou H-W, et al. Airway delivery of bone marrow–derived mesenchymal stem cells reverses bronchopulmonary dysplasia superimposed with acute respiratory distress syndrome in an infant. Cell Med. 2018;10:2155179018759434.
   Web of Science ®Google Scholar
• O’Reilly M, Mobius MA, Vadivel A, et al. Late rescue therapy with cord-derived mesenchymal stromal cells for established lung injury in experimental bronchopulmonary dysplasia. Stem Cells Dev. 2020;29(6):364–371.
   Web of Science ®Google Scholar
• Nardiello C, Mizikova I, Morty RE. Looking ahead: where to next for animal models of bronchopulmonary dysplasia? Cell Tissue Res. 2017;367(3):457–468. Epub 2016/ 12/06.
   Web of Science ®Google Scholar
• Willis GR, Kourembanas S, Mitsialis SA. Toward exosome-based therapeutics: isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med. 2017;4:63. Epub 2017/ 10/25.
   PubMed Web of Science ®Google Scholar
• Álvarez-Fuente M, Arruza L, Lopez-Ortego P, et al. Off-label mesenchymal stromal cell treatment in two infants with severe bronchopulmonary dysplasia: clinical course and biomarkers profile. Cytotherapy. 2018;20(11):1337–1344.
   Web of Science ®Google Scholar
• Stocks J, Hislop A, Sonnappa S. Early lung development: lifelong effect on respiratory health and disease. Lancet Respir Med. 2013;1(9):728–742. Epub 2014/ 01/17.
   PubMed Web of Science ®Google Scholar
• Perez Tarazona S, Solano Galan P, Bartoll Alguacil E, et al. Bronchopulmonary dysplasia as a risk factor for asthma in school children and adolescents: a systematic review. Allergol Immunopathol (Madr). 2018;46(1):87–98. Epub 2017/ 07/03.
   Web of Science ®Google Scholar
• Schmalisch G, Wilitzki S, Roehr CC, et al. Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: longitudinal assessment during the first 15 months of corrected age. BMC Pediatr. 2012;12:37. Epub 2012/ 03/27.
   Web of Science ®Google Scholar
• Postma DS, Bush A, van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet. 2015;385(9971):899–909. Epub 2014/ 08/16.
   PubMed Web of Science ®Google Scholar
• Kim Y-S, Kim J-Y, Cho R, et al. Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway. Exp Mol Med. 2017;49(1):e284–e.
   Web of Science ®Google Scholar
• Klinger JR, Pereira M, Del Tatto M, et al. Mesenchymal stem cell extracellular vesicles reverse sugen/hypoxia pulmonary hypertension in rats. Am J Respir Cell Mol Biol. 2020;62(5):577–587. doi:10.1165/rcmb.2019-0154OC. Epub 2019/ 11/14.
   Google Scholar
• Yoder HE, Braun RK, Sobotik A, et al. Increased activation of M2 macrophages in 1 year-old rat lungs following neonatal hyperoxia exposure. Faseb J. 2017;31(1): 872.3-.3.
   Google Scholar
• Chen W, Huang Y, Han J, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res. 2016;64(4):831–840. Epub 2016/ 04/27.
   PubMed Web of Science ®Google Scholar
• Willis GR, Fernandez-Gonzalez A, Reis M, et al. Macrophage immunomodulation: the gatekeeper for mesenchymal stem cell derived-exosomes in pulmonary arterial hypertension? Int J Mol Sci. 2018;19(9). Epub 2018/ 08/29. DOI:10.3390/ijms19092534.
   Web of Science ®Google Scholar
• Kordelas L, Schwich E, Dittrich R, et al. Individual immune-modulatory capabilities of MSC-derived extracellular vesicle (EV) preparations and recipient-dependent responsiveness. Int J Mol Sci. 2019;20(7):1642.
   Web of Science ®Google Scholar
• Phinney DG, Di Giuseppe M, Njah J, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nature Commun. 2015;6:8472.
   PubMed Web of Science ®Google Scholar
• Jackson MV, Morrison TJ, Doherty DF, et al. Mitochondrial transfer via tunneling nanotubes is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS. Stem Cells. 2016;34(8):2210–2223.
   PubMed Web of Science ®Google Scholar