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

• Published in: Stem cells translational medicine Vol. 8; no. 4; pp. 344 - 354
• Main Authors: Xu, Siguang, Liu, Cong, Ji, Hong‐Long
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2019; Oxford University Press
• Subjects: Animals; Antioxidants; Apoptosis; B cells; Cell activation; Cell‐Based Drug Development, Screening, and Toxicology; Complications and side effects; Cytokines; Disease Progression; Exosome; Exosomes; Exosomes - physiology; Extracellular matrix; Extracellular vesicles; Extracellular Vesicles - physiology; Fibroblasts; Growth factors; Humans; Immune response; Inflammation; Lung cancer; Lung diseases; Lung fibrosis; Lung Injury - pathology; Lung Injury - therapy; Lungs; Medical prognosis; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchyme; Metastases; Paracrine signalling; Radiation; Radiation Injuries - therapy; Radiation pneumonitis; Radiation therapy; Radiotherapy; Regeneration - physiology; Respiratory function; Secretome; Signal transduction; Stem cells; Thorax; Translation; Tumors; Secretome; Exosome; Lung fibrosis; Mesenchymal stem cells; Radiation pneumonitis
• ISSN: 2157-6564; 2157-6580; 2157-6580
• DOI: 10.1002/sctm.18-0038

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 Mesenchymal stem cells regulate inflammatory signaling, fibrotic response, and immune cells to attenuate RILI in injured lung tissue environment via secreting an array of soluble factors.