Mesenchymal stem cell-based therapy for radiation-induced lung injury

166

168

During acute or chronic lung injury, inappropriate immune response and/or aberrant repair process causes irreversible damage in lung tissue and most usually results in the development of fibrosis followed by decline in lung function. Inhaled corticosteroids and other anti-inflammatory drugs are very effective in patients with inflammatory lung disorders, but their long-term use is associated with severe side effects. Accordingly, new therapeutic agents that will attenuate ongoing inflammation and, at the same time, promote regeneration of injured alveolar epithelial cells are urgently needed. Mesenchymal stem cells (MSCs) are able to modulate proliferation, activation, and effector function of all immune cells that play an important role in the pathogenesis of acute and chronic inflammatory lung diseases. In addition to the suppression of lung-infiltrated immune cells, MSCs have potential to differentiate into alveolar epithelial cells in vitro and, accordingly, represent new players in cell-based therapy of inflammatory lung disorders. In this review article, we described molecular mechanisms involved in MSC-based therapy of acute and chronic pulmonary diseases and emphasized current knowledge and future perspectives related to the therapeutic application of MSCs in patients suffering from acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, and idiopathic pulmonary fibrosis.

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives

Harrell

Sadikot

Pascual

et al. 2019

166

168

“…and MSCs, which have been used in clinical trials as therapeutics and are becoming increasingly important for alleviating irradiated tissue damage. To date, no significant improvement has been found in clinical trials of MSC-based therapy with anti-inflammatory agents and antibiotics for RILI [ 46 ]. Although nintedanib treatment attenuates tissue fibrosis after RILI [ 16 ], our results show that nintedanib used on irradiated alveolar epithelium was not beneficial for the attenuation of regenerative lung cells.…”

Section: Discussionmentioning

confidence: 99%

Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells

Wang

Hong

et al. 2020

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.

“…In 2006, the international association of cell therapy (International Society for Cellular Therapy, ISCT) unified the definition of MSCs as follows: (1) adherent growth; (2) cell surface expression of certain specific antigens (markers); and (3) fat cell, osteoblast, and chondrocyte differentiation ability [ 62 ]. Since then, increasing evidence has shown that MSCs play an important role in tissue repair, regeneration, and immune regulation [ 63 – 66 ]. Now, the definition of MSCs has been extended, and the concept of “MSCs” as nonhematopoietic stem cells in the bone marrow was borrowed from the hypothesis of BMSCs but extended to nonskeletal tissue.…”

Section: Current Strategies For Articular Cartilage Regenerationmentioning

confidence: 99%

Clinical Application Status of Articular Cartilage Regeneration Techniques: Tissue-Engineered Cartilage Brings New Hope

Jiang

Guo

Tian

et al. 2020

Hyaline articular cartilage lacks blood vessels, lymphatics, and nerves and is characterised by limited self-repair ability following injury. Traditional techniques of articular cartilage repair and regeneration all have certain limitations. The development of tissue engineering technology has brought hope to the regeneration of articular cartilage. The strategies of tissue-engineered articular cartilage can be divided into three types: “cell-scaffold construct,” cell-free, and scaffold-free. In “cell-scaffold construct” strategies, seed cells can be autologous chondrocytes or stem. Among them, some commercial products with autologous chondrocytes as seed cells, such as BioSeed®-C and CaReS®, have been put on the market and some products are undergoing clinical trials, such as NOVOCART® 3D. The stem cells are mainly pluripotent stem cells and mesenchymal stem cells from different sources. Cell-free strategies that indirectly utilize the repair and regeneration potential of stem cells have also been used in clinical settings, such as TruFit and MaioRegen. Finally, the scaffold-free strategy is also a new development direction, and the short-term repair results of related products, such as NOVOCART® 3D, are encouraging. In this paper, the commonly used techniques of articular cartilage regeneration in surgery are reviewed. By studying different strategies and different seed cells, the clinical application status of tissue-engineered articular cartilage is described in detail.