Loy H, Kuok DIT, Hui KPY, Choi MHL, Yuen W. Therapeutic implications of human umbilical cord mesenchymal stromal cells in attenuating influenza A/H5N1-associated acute lung injury. J Infect Dis. 2018 Aug 2.
Background:
Highly pathogenic avian influenza viruses can cause severe forms of acute lung injury (ALI) in humans, where pulmonary flooding leads to respiratory failure. Therapeutic benefits of bone-marrow mesenchymal stromal cells (BM-MSCs) have been demonstrated in an influenza H5N1 ALI model. However, clinical translation is impractical and limited by declining efficacy with increase in donor age. Umbilical cord MSCs (UC-MSCs) are easier to obtain in comparison, and their primitive source may offer more potent therapeutic effects.
Methods:
Here we investigate the therapeutic efficacy of UC-MSCs on mechanisms of pulmonary oedema formation; alveolar fluid clearance (AFC) and protein permeability (APP), of H5N1-infected human alveolar epithelial cells (AECs). UC-MSCs were also tested in a mouse model of influenza ALI.
Results:
We found that UC-MSCs were effective in restoring impaired AFC and APP of H5N1-infected AECs. UC-MSCs consistently outperformed BM-MSCs, partly due to greater growth factor secretion of angiopoietin-1 and hepatocyte growth factor. Conditioned UC-MSC medium and UC-MSC exosomes were also able to recapitulate these effects. However, UC-MSCs only slightly improved survival of H5N1-infected mice.
Conclusions:
Our results suggest that UC-MSCs are effective in restoring AFC and APP in H5N1-associated ALI and confer functional in addition to practical advantages over conventional BM-MSCs.
Highly pathogenic avian influenza viruses can cause severe forms of acute lung injury (ALI) in humans, where pulmonary flooding leads to respiratory failure. Therapeutic benefits of bone-marrow mesenchymal stromal cells (BM-MSCs) have been demonstrated in an influenza H5N1 ALI model. However, clinical translation is impractical and limited by declining efficacy with increase in donor age. Umbilical cord MSCs (UC-MSCs) are easier to obtain in comparison, and their primitive source may offer more potent therapeutic effects.
Methods:
Here we investigate the therapeutic efficacy of UC-MSCs on mechanisms of pulmonary oedema formation; alveolar fluid clearance (AFC) and protein permeability (APP), of H5N1-infected human alveolar epithelial cells (AECs). UC-MSCs were also tested in a mouse model of influenza ALI.
Results:
We found that UC-MSCs were effective in restoring impaired AFC and APP of H5N1-infected AECs. UC-MSCs consistently outperformed BM-MSCs, partly due to greater growth factor secretion of angiopoietin-1 and hepatocyte growth factor. Conditioned UC-MSC medium and UC-MSC exosomes were also able to recapitulate these effects. However, UC-MSCs only slightly improved survival of H5N1-infected mice.
Conclusions:
Our results suggest that UC-MSCs are effective in restoring AFC and APP in H5N1-associated ALI and confer functional in addition to practical advantages over conventional BM-MSCs.
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