Abstract
Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Adipose tissue-derived stem cells (ADSCs) are useful for ameliorating lung injury in animal models. However, whether ADSCs differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and 129Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.
Highlights
Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues [1, 2]
Positive staining with oil red O, alkaline phosphatase, and alcian blue indicated that Adipose tissue-derived stem cells (ADSCs) could differentiate into adipocytes, osteocytes, and chondrocytes, respectively (Figure 1(a))
Immunohistochemistry showed that green fluorescent protein- (GFP-)positive ADSCs accumulated in the emphysematous lungs, and some of the engrafted ADSCs were positive for an alveolar epithelial marker, such as transcription factor-1 (TTF-1), surfactant protein B (SPB), and surfactant protein C (SPC) at day 7 (Figure 3(a))
Summary
Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from various tissues [1, 2]. Treatment using MSCs can induce tissue repair by self-renewal, differentiation, and paracrine effects with immunomodulatory properties and anti-inflammatory and angiogenic actions [3]. Adipose tissue-derived stem cells (ADSCs) were first identified as MSCs in adipose tissue in 2001 [4]. ADSCs rapidly proliferate and secrete high amounts of regeneration promoting factors [5]. The therapeutic utility of ADSCs has been studied in various diseases [6]. Cellular therapy using ADSCs can induce recovery from injuries such as myocardial infarction [7], cerebral ischemia, and cerebral reperfusion after ischemia [8, 9] and spinal cord injury in animal models [10]. Previous studies reported that ADSCs have the ability to home, immunomodulate, promote repair, and induce direct regeneration of damaged tissue
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