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Review
. 2019 Apr;8(4):344-354.
doi: 10.1002/sctm.18-0038. Epub 2019 Jan 7.

Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses

Siguang Xu  1 , Cong Liu  1 , Hong-Long Ji  2   3
Affiliations
Review

Concise Review: Therapeutic Potential of the Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Radiation-Induced Lung Injury: Progress and Hypotheses

Siguang Xu et al. Stem Cells Transl Med. 2019 Apr.

Abstract

Radiation-induced lung injury (RILI) is a common complication in radiotherapy of thoracic tumors and limits the therapeutic dose of radiation that can be given to effectively control tumors. RILI develops through a complex pathological process, resulting in induction and activation of various cytokines, infiltration by inflammatory cells, cytokine-induced activation of fibroblasts, and subsequent tissue remodeling by activated fibroblasts, ultimately leading to impaired lung function and respiratory failure. Increasing evidence shows that mesenchymal stem cells (MSCs) may play a main role in modulating inflammation and immune responses, promoting survival and repair of damaged resident cells and enhancing regeneration of damaged tissue through soluble paracrine factors and therapeutic extracellular vesicles. Therefore, the use of the MSC-derived secretome and exosomes holds promising potential for RILI therapy. Here, we review recent progress on the potential mechanisms of MSC therapy for RILI, with an emphasis on soluble paracrine factors of MSCs. Hypotheses on how MSC derived exosomes or MSC-released exosomal miRNAs could attenuate RILI are also proposed. Problems and translational challenges of the therapies based on the MSC-derived secretome and exosomes are further summarized and underline the need for caution on rapid clinical translation. Stem Cells Translational Medicine 2019;8:344-354.

Keywords: Exosome; Lung fibrosis; Mesenchymal stem cells; Radiation pneumonitis; Secretome.

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Conflict of interest statement

The authors indicated no potential conflicts of interest.

Figures

Figure 1
Figure 1
Mesenchymal stem cells (MSCs) regulate inflammatory signaling, fibrotic response and immune cells to attenuate radiation‐induced lung injury (RILI) via secreting an array of soluble factors. Radiation causes delayed damage to resident lung cells, leading primarily to the injury; however, MSCs can protect injured lung cells against ROS via secreting superoxide dismutases including SOD1 and SOD3. Radiation can also stimulate lung fibroblasts to differentiate into myofibroblasts. Myofibroblasts can further promote the synthesis of additional collagens, leading to excessive deposition and abnormal remodeling of the extracellular matrix, which is a hallmark of RILI. MSCs may inhibit lung myofibroblasts via secreting HGF and PGE2. Moreover, radiation can also activate proinflammatory signaling pathways and trigger the recruitment of various immune cells into the lung, such as monocytic cells, neutrophils, and lymphocytes. MSCs can inhibit proinflammatory signaling and immune cell activation via secreting soluble receptors and various cytokines including sTβR, sIL1RN, TNFR1, VEGF, KGF, EGF, IL‐10, TSG6, IL‐6, HGF, PGE2, and so forth.
Figure 2
Figure 2
The anti‐inflammatory and antifibrogenic potential of mesenchymal stem cells (MSCs) released exosomal miRNAs. In the RILI microenvironment, MSCs actively release miRNAs by exosomal transportation, which are taken up by recipient cells including injured endothelial cells, immune cells, myofibroblast, fibroblast, and so forth. These activities can downregulate IL‐β, IL‐6, and TNF‐α by targeting the mRNA of proinflammatory and profibrogenic genes including TLR4, TGF‐β, Smad2, and so forth, and then attenuate radiation‐induced lung injury.
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