Hepatocyte Growth Factor and Insulin-like Growth Factor-1 based Cellular Therapies for Oxidative Stress Injury

Abstract

: Imbalance between free radicals and antioxidants causes oxidative stress by the accumulation of reactive oxygen species (ROS) in the tissues and organs. Oxidative stress occurs in many damage conditions, and the increase of ROS and reduction of antioxidants enhances inflammation, apoptosis, fibrosis and may worsen the pathology leading to organ failure. The potential therapies aim to increase antioxidants and decrease ROS. Mesenchymal stem cells (MSCs) isolated from the stroma of various tissues are multipotent cells and have beneficial effects on several diseases with their immunomodulation and regeneration capacities. MSCs trigger the proliferation of the cells with various secretory factors, reduce the oxidative stress and decrease apoptosis, inflammation, fibrosis and thus increase the regeneration. However, survival, engraftment and differentiation problems of transplanted MSCs restrict their protective and regenerative effects. Preconditioning of MSCs with several factors such as cytokines, hypoxia, chemical agents, pharmocological drugs, physical factors and growth factors enhances their repairing efficacy for injury and disease models. This review is mainly focused on insulin-like growth factor (IGF-1) and hepatocyte growth factor (HGF), and discusses the research on MSC priming/induction with IGF-1 and HGF stimulation either by supplementation or overexpression can enhance regenerative potential of MSCs on various oxidative stress conditions such as acute/chronic kidney diseases, lung injury, cancer, metabolic and cardiovascular diseases.

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

“…However, senescence is not simply the result of the increasing age, but also the result of the innate reaction under pathological conditions, such as chronic injury [ 28 ]. In recent decades, IGF1 has become a research focus, not only because inactivating the IGF1 signaling pathway can prolong life, but also because activating this signaling pathway would release inflammatory factors, aggravate the oxidative stress response and other pathological conditions, and jointly accelerate cell senescence [ 29 ]. However, it is not clear whether IGF1 is an important cause of AEC senescence in IPF.…”

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins

“…The present study showed that there is need for adjustment of the application. Since it is possible to produce IGF-1 overexpressing stem cells [93], their circadian release may be one option to further investigate. Drug delivery via ROS-responsible nanoparticles represents another promising option [94].…”

Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis

“…Secondly, SOD-MSCs can reduce the inflammation in the skin through the JAK-STAT pathway ( 54 ). In psoriasis, another research found that subcutaneous administration of SOD-MSCs (UC-MSCs) in mice (2 × 10 6 cells) can ameliorate the symptoms of skin lesion by regulating the inflammatory pathways including toll-like receptor-7, nuclear factor-kappa B(NFκB), p38 mitogen-activated kinase (MAPK), and JAK-STAT pathways ( 71 ) ( Figure 2 ). Other studies indicate that hepatocyte growth factor-transduced MSCs (HGF-MSCs) also exert a better capability of antioxidant response in various acute/chronic disease ( 58 ).…”