Abstract
Less quantity of transplanted mesenchymal stem cells (MSCs) influences the therapeutic effects on radiation-induced lung injury (RILI). Previous studies have demonstrated that MSCs overexpressing Chemokine (C-X-C motif) receptor 4 (CXCR4) could increase the quantity of transplanted cells to local tissues. In the present study, we conducted overexpressing CXCR4 human umbilical cord mesenchymal stem cell (HUMSC) therapy for RILI. C57BL mice received single dose of thoracic irradiation with 13 Gy of X-rays and then were administered saline, control HUMSCs, or CXCR4-overexpressing HUMSCs via tail vein. Transfection with CXCR4 enhanced the quantity of transplanted HUMSCs in the radiation-induced injured lung tissues. CXCR4-overexpressing HUMSCs not only improved histopathological changes but also decreased the radiation-induced expression of SDF-1, TGF-β1, α-SMA, and collagen I and inhibited the radiation-induced decreased expression of E-cadherin. Transplanted CXCR4-overexpressing HUMSCs also could express pro-SP-C, indicated adopting the feature of ATII. These finding suggests that CXCR4-overexpressing HUMSCs enhance the protection against RILI and may be a promising strategy for RILI treatment.
Highlights
Radiotherapy, the commonly used treatment for thoracic malignant tumor, can lead to severe complications in some patients, like radiation-induced lung injury (RILI)
Most of the human umbilical cord mesenchymal stem cell (HUMSC) appeared spindle-shaped under light microscopy, and after 3 weeks of culture, the quantity of HUMSCs increased and they aggregated like a vortex (Supplementary Figure 1(a))
A flow cytometric analysis presented that HUMSCs were positive for CD29, CD44, and CD90 and were negative for CD31, CD34, CD45, and HLA-DR, which is consistent with previous reports [29,30,31] (Supplementary Figure 1(b))
Summary
Radiotherapy, the commonly used treatment for thoracic malignant tumor, can lead to severe complications in some patients, like radiation-induced lung injury (RILI). RILI may include early radiation-induced pneumonitis and advanced stage radiation-induced lung fibrosis [1]. They can affect the patient’s quality of life with severe adverse complications [2]. The incidence rate of severe irradiation-induced lung injuries reported is 15% among patients treated by thoracic radiotherapy [4]. These patients are presented with symptoms such as cough, panting, dyspnea, and even respiratory failure [5, 6]. As there were few efficient therapeutic methods available for RILI in clinical practice [7], it is critical to understand the complications in great depth and investigate better methods of protection to improve patients’ life quality
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