Mesenchymal Stromal Cells: Current Understanding and Clinical Status

Mesenchymal Stromal Cells: Current Understanding and Clinical Status

2010 | HUSEIN K. SALEM, CHRIS THIEMERMANN
Mesenchymal stromal cells (MSCs) are multipotent cells that can be isolated from various adult tissues and have the potential to differentiate into diverse cell lineages. They possess immunosuppressive properties, suppressing T-cell and NK cell functions, and modulating dendritic cell activities. MSCs have shown beneficial effects in tissue repair and regeneration, and their ability to home to injured tissues and modulate inflammatory responses makes them promising for clinical applications. Preclinical studies have demonstrated their potential in cardiovascular and renal applications, and clinical trials are ongoing to evaluate their efficacy. MSCs are characterized by their ability to adhere to plastic under standard culture conditions, express specific surface markers, and differentiate into osteocytes, adipocytes, and chondrocytes. Despite their potential, the exact mechanisms by which MSCs exert their effects remain unclear. MSCs can be isolated from various tissues, including bone marrow, adipose tissue, liver, muscle, amniotic fluid, placenta, umbilical cord blood, and dental pulp. However, bone marrow remains the principal source for most preclinical and clinical studies. MSCs have the ability to home to sites of tissue injury following intravenous injection, which is facilitated by chemokine gradients and the SDF-1/CXCR4 axis. They also express various adhesion molecules that respond to chemokines, enabling them to migrate to sites of injury. Integrins and other receptors also play a role in MSC homing and engraftment. The homing efficiency of MSCs is influenced by isolation and culture protocols, and subculturing can affect their phenotype and homing ability. MSCs have immunomodulatory properties, suppressing T-cell proliferation and modulating the immune response. They can inhibit T-cell activation by reducing the expression of costimulatory molecules and promoting the production of anti-inflammatory cytokines. MSCs also inhibit the maturation of dendritic cells, which can reduce the immune response. Additionally, MSCs can inhibit the proliferation of natural killer (NK) cells through cell-cell contact and the secretion of soluble factors. In renal disease, MSCs have shown potential in promoting tissue repair and reducing inflammation. Studies have demonstrated that MSCs can home to injured kidneys and facilitate repair, and they have been shown to inhibit the proliferation of T-cells and reduce inflammation. In cardiovascular disease, MSCs have shown potential in promoting angiogenesis and reducing fibrosis. MSCs can engraft in the damaged heart and differentiate into cardiac myocytes, improving cardiac function. MSC-based therapies are being explored in clinical trials for various conditions, including graft-versus-host disease, Crohn's disease, and other hematologic and autoimmune disorders. The therapeutic potential of MSCs is being evaluated in phase I/II and III clinical trials, with promising results in improving cardiac function and reducing inflammation. However, the exact mechanisms by which MSCs exert their effects remain unclear, and further research is needed to fully understand theirMesenchymal stromal cells (MSCs) are multipotent cells that can be isolated from various adult tissues and have the potential to differentiate into diverse cell lineages. They possess immunosuppressive properties, suppressing T-cell and NK cell functions, and modulating dendritic cell activities. MSCs have shown beneficial effects in tissue repair and regeneration, and their ability to home to injured tissues and modulate inflammatory responses makes them promising for clinical applications. Preclinical studies have demonstrated their potential in cardiovascular and renal applications, and clinical trials are ongoing to evaluate their efficacy. MSCs are characterized by their ability to adhere to plastic under standard culture conditions, express specific surface markers, and differentiate into osteocytes, adipocytes, and chondrocytes. Despite their potential, the exact mechanisms by which MSCs exert their effects remain unclear. MSCs can be isolated from various tissues, including bone marrow, adipose tissue, liver, muscle, amniotic fluid, placenta, umbilical cord blood, and dental pulp. However, bone marrow remains the principal source for most preclinical and clinical studies. MSCs have the ability to home to sites of tissue injury following intravenous injection, which is facilitated by chemokine gradients and the SDF-1/CXCR4 axis. They also express various adhesion molecules that respond to chemokines, enabling them to migrate to sites of injury. Integrins and other receptors also play a role in MSC homing and engraftment. The homing efficiency of MSCs is influenced by isolation and culture protocols, and subculturing can affect their phenotype and homing ability. MSCs have immunomodulatory properties, suppressing T-cell proliferation and modulating the immune response. They can inhibit T-cell activation by reducing the expression of costimulatory molecules and promoting the production of anti-inflammatory cytokines. MSCs also inhibit the maturation of dendritic cells, which can reduce the immune response. Additionally, MSCs can inhibit the proliferation of natural killer (NK) cells through cell-cell contact and the secretion of soluble factors. In renal disease, MSCs have shown potential in promoting tissue repair and reducing inflammation. Studies have demonstrated that MSCs can home to injured kidneys and facilitate repair, and they have been shown to inhibit the proliferation of T-cells and reduce inflammation. In cardiovascular disease, MSCs have shown potential in promoting angiogenesis and reducing fibrosis. MSCs can engraft in the damaged heart and differentiate into cardiac myocytes, improving cardiac function. MSC-based therapies are being explored in clinical trials for various conditions, including graft-versus-host disease, Crohn's disease, and other hematologic and autoimmune disorders. The therapeutic potential of MSCs is being evaluated in phase I/II and III clinical trials, with promising results in improving cardiac function and reducing inflammation. However, the exact mechanisms by which MSCs exert their effects remain unclear, and further research is needed to fully understand their
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