Abstract
Radiation therapy is one of the most important treatment modalities for thoracic tumors. Despite significant advances in radiation techniques, radiation-induced lung injury (RILI) still occurs in up to 30% of patients undergoing thoracic radiotherapy, and therefore remains the main dose-limiting obstacle. RILI is a potentially lethal clinical complication of radiotherapy that has 2 main stages: an acute stage defined as radiation pneumonitis, and a late stage defined as radiation-induced lung fibrosis. Patients who develop lung fibrosis have a reduced quality of life with progressive and irreversible organ malfunction. Currently, the most effective intervention for the treatment of lung fibrosis is lung transplantation, but the lack of available lungs and transplantation-related complications severely limits the success of this procedure. Over the last few decades, advances have been reported in the use of mesenchymal stem cells (MSCs) for lung tissue repair and regeneration. MSCs not only replace damaged lung epithelial cells but also promote tissue repair through the secretion of anti-inflammatory and anti-fibrotic factors. Here, we present an overview of MSC-based therapy for radiation-induced lung fibrosis, focusing in particular on the molecular mechanisms involved and describing the most recent preclinical and clinical studies carried out in the field.
Highlights
Radiation therapy is one of the most important treatment modalities for thoracic tumors such as lymphoma and lung, breast and esophageal cancer [1,2]
UC-mesenchymal stem cells (MSCs) from humans proved effective in a rat model of radiation pneumonitis [199], while adipose tissue-derived MSCs (AD-MSCs) infused into a mouse model of acute radiation pneumonitis prolonged survival and decreased levels of inflammatory and fibrotic mediators [200]
There is currently only one active phase I study on the clinical use of UC-MSCs in post-radiotherapy pulmonary fibrosis, indicating that there is still a long way to go before MSCs-based therapy can be implemented in clinical practice for radiation-induced lung injury (RILI) (Figure 6)
Summary
Radiation therapy is one of the most important treatment modalities for thoracic tumors such as lymphoma and lung, breast and esophageal cancer [1,2]. Mesenchymal stem cells (MSCs) represent a subpopulation currently defined by minimal criteria as having plastic adherence properties and the potential for in vitro trilineage differentiation to adipocytes, chondroblasts, and osteoblasts [10]. Over the past few decades, interest in the clinical potential of MSCs in regenerative medicine has significantly increased Their relatively easy access, isolation and expansion ex vivo, as well as their ability to repair tissues and modulate immune and stromal cell functions displaying anti-fibrotic activity have aroused the interest of researchers, making MSC-based therapy a promising candidate for many cell-based therapies, including the treatment of RILI
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