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Treating Neonatal Lung Injury via the Intranasal Administration of MSCs

Review of “Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia” from STEM CELLS Translational Medicine by Stuart P. Atkinson

We currently lack adequate treatment options for the lung disease bronchopulmonary dysplasia, which represents the most common cause of death in premature neonates. Given their immunomodulatory capabilities and ability to restore function and lung epithelial/endothelial integrity [1, 2], multiple preclinical studies have evaluated the therapeutic potential of the intratracheal or intravenous administration of mesenchymal stem cells (MSCs) in neonatal lung injury in animal models [3].

Now, researchers from the laboratory of Alvaro Moreira (University of Texas, San Antonio, T, USA) sought to further advance this therapeutic strategy by evaluating the feasibility of intranasal delivery of human umbilical cord tissue MSCs to neonatal rat pups as a clinically relevant and non-invasive approach to deliver multiple doses and the potential of this approach to attenuate lung injury in experimental bronchopulmonary dysplasia. These findings, reported in STEM CELLS Translational Medicine, provide evidence of the potential relevance of intranasal delivery of umbilical cord MSCs in the treatment of human patients in the future [4].

Here are the fascinating details of this fascinating new study from Moreira et al. - 

  • Following hypoxia-induced bronchopulmonary dysplasia, rats received multiple intranasal doses of umbilical cord tissue MSCs that displayed the characteristic cell surface antigens and possessed trilineage differentiation potential
    • The immunohistochemical detection of a human mitochondrial antibody provided evidence of human umbilical cord MSC migration to the injured rat lungs 
  • Additional histological analyses established that all animals treated with MSCs displayed restored lung alveolarization, vascularization, and pulmonary vascular remodeling
    • However, the authors found no evidence for alterations to pulmonary vessel muscularization, cardiac remodeling, or fibrosis
  • Gene and protein analysis suggested that the therapeutic effect of MSCs derived from enhanced angiogenesis (VEGF), immunomodulation (CX3CL1, TNFα, TIM‐1, hepassocin, neprilysin), cell survival (osteoprotegerin), and wound healing (MMP‐2, LIF)

Overall, the authors demonstrate that the intranasal administration of human umbilical cord tissue MSCs represents a feasible and effective means to restore lung alveolar growth and vascular development in a rat model of bronchopulmonary dysplasia. The authors hope that further evaluations will allow the intranasal delivery of MSCs to be employed separately or as an adjunct/alternative to other routes as an advanced treatment option for premature neonates.

For more on MSC-based treatments for neonatal lung injury, stay tuned to the Stem Cells Portal!

References

  1. Gupta N, Su X, Popov B, et al., Intrapulmonary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Survival and Attenuates Endotoxin-Induced Acute Lung Injury in Mice. The Journal of Immunology 2007;179:1855.
  2. Fang X, Neyrinck AP, Matthay MA, et al., Allogeneic Human Mesenchymal Stem Cells Restore Epithelial Protein Permeability in Cultured Human Alveolar Type II Cells by Secretion of Angiopoietin-1. Journal of Biological Chemistry 2010;285:26211-26222.
  3. Bernardo ME, Pagliara D, and Locatelli F, Mesenchymal stromal cell therapy: a revolution in Regenerative Medicine? Bone Marrow Transplantation 2012;47:164-171.
  4. Moreira A, Winter C, Joy J, et al., Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia. STEM CELLS Translational Medicine 2020;9:221-234.