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

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

Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome

“…Accumulating evidence suggest that MSC-sourced CM and Exos may represent a compelling alternative to MSCs in the treatment of ALF and liver fibrosis (Table 1) [13,14,15,16,17,18,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88].…”

“…Beneficial effects of MSC-CM and MSC-Exo-based therapy have been demonstrated in the animal models of ALI, asthma, COPD and IPF (Table 2) [19,20,21,22,83,84,85,86,87,88,89,90,91]. Importantly, MSC-CM and MSC-EVs managed to induce regeneration of injured epithelium, attenuation of inflammation and fibrosis in the lungs in similar manner as transplanted MSCs [19,24,84,85,86,87].…”

Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase

“…These small vesicles are widely involved in intercellular communication and can alter the metabolism of target cells or local tissue microenvironment. Recently, MSC-derived exosomes were shown to mediate the therapeutic efficacy of MSCs in various disorders, such as acute kidney injury ( 26 ), cardiovascular disease ( 27 ), lung injury ( 28 ), radiation-induced hematopoietic failure ( 29 ), and liver diseases ( 30 ). However, high amounts of MSC-CM are required to obtain a small concentration of exosomes.…”

Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity

“…MSCs regenerative properties are mediated by their ability to infiltrate and engraft injured areas, where they reduce inflammation, promote angiogenesis, prevent apoptosis, improve scar formation, and mediate tissue remodeling via the paracrine secretion of chemokines and growth factors (227,228). These pluripotent stem cells are capable of reprogramming into differentiated phenotypes participating in regenerative and reparative programs of most tissues and organs (229)(230)(231)(232)(233)(234).…”