Abstract
Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34+ progenitor cells (fCB-CD34+ cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34+ cells were transplanted i.v. to mice while CD34− cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34+ cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34− cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34+ cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34− cell-treated controls. Importantly, lung inflammation in fCB-CD34+ cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34− cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34+ cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2′-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34+ cell-treated mice at 52 h post-LPS compared to PBS or CD34− cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34+ cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34+ cells are an important source of stem cells for the treatment of acute lung injury.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain one of the most common causes of acute respiratory failure in critically ill patients [1]
Isolated human CD34+ progenitor cells inhibit lung vascular injury following LPS challenge Human CD34+ progenitor cells were isolated from human umbilical cord blood using the immunomagnetic beads with purity of routinely greater than 95% (Fig. 1A)
We have investigated the effects of intravenous administration of freshly isolated human umbilical cord blood CD34+ progenitor cells on LPS-induced lung injury in mice
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain one of the most common causes of acute respiratory failure in critically ill patients [1]. Human mesenchymal stem or stromal cells (MSC) are shown to be protective in animal models of ALI induced by lipopolysaccharide (LPS) [5,6,7,8], live bacteria [9,10], polymicrobial sepsis [8,11], and pneumonia [10] as well as in an ex vivo perfused human lung injury model challenged with E. coli [12,13] These studies suggest that human adult stem cells is a potential therapeutic approach for the treatment of ALI and ARDS [14,15].
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