Mesenchymal stem cells (MSCs) are multipotent stem cells characterized by their robust proliferative capacity, homing ability, differentiation potential, and low immunogenicity in vitro. MSCs can be isolated from a variety of tissues, primarily including but not limited to bone marrow, adipose tissue, umbilical cord, placenta, and dental pulp. Although there have been a large number of clinical studies on the treatment of diseases by MSCs and MSCs-derived exosomes (MSCs-EXO), the large-scale clinical application of MSCs and MSCs-EXO have been limited due to the heterogeneity of the results among various studies. This review provides a detailed description of the classification and characterization of MSCs and MSCs-EXO, as well as their extraction methods. Furthermore, this review elaborates on three key mechanisms of MSCs and MSCs-EXO: paracrine mechanisms, immunomodulatory and anti-inflammatory effects, as well as their promotion of tissue regeneration. This review also examines the role of MSCs and MSCs-EXO in cardiovascular diseases, neurological disorders, autoimmune diseases, musculoskeletal disorders, and other systemic diseases over the past five years, while discussing the challenges and difficulties associated with their clinical application. Finally, we systematically summarized and analyzed the potential causes of the various heterogeneous results currently observed. Additionally, we provided an in-depth discussion on the challenges and opportunities associated with the clinical translation of disease treatment approaches based on MSCs, MSCs-EXO, and engineered exosomes.

In recent years, the use of thrombolytic therapy for treating ischemia/reperfusion injury has resulted in damage to the self‑regulatory mechanisms of the brain. This is due to the increased production of free radicals, excitatory amino acids and pro‑inflammatory cytokines causing secondary damage to the brain. Simple thrombolytic therapy has not been the best approach for treating ischemia/reperfusion injury. Excessive perfusion leads to failure of the body's self‑regulatory functions, which in turn increases the area of cerebral edema and aggravates cerebral ischemia. Previous studies have evaluated the satiety hormone leptin as a link between energy expenditure and obesity. Of note, leptin, which is involved in brain development, synaptic transmission and angiogenesis following ischemia/reperfusion injury, has been considered an important factor for treating ischemia/reperfusion injury. The present review outlines the discovery of leptin and discusses its association with cerebral ischemia/reperfusion.

Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases.