Preconditioning with Substance P Restores Therapeutic Efficacy of Aged ADSC by Elevating TNFR2 and Paracrine Potential.

Aging leads to a decline in stem cell activity by reducing the repopulation rate and paracrine potential, ultimately diminishing efficacy in vivo. TNF-α can exert inflammatory and cell death actions via Erk by binding to TNFR-1, and survival and tissue repair actions via Akt by binding to TNFR-2. Aged cells are reported to have insufficient expression of TNFR-2, indicating that aged adipose-derived stem cells (ADSCs-E) lack the ability for cell survival and immune control compared to young ADSCs (ADSCs-Y).

Substance P-Mediated Vascular Protection Ameliorates Bone Loss.

Estrogen deficiency causes bone loss via diverse pathological cellular events. The involvement of the vasculature in bone formation has been widely studied, and type H vasculature has been found to be closely related to bone healing. Ovariectomy- (OVX-) induced estrogen deficiency reduces type H vessel density and promotes reduction of bone density.

Substance-P Inhibits Cardiac Microvascular Endothelial Dysfunction Caused by High Glucose-Induced Oxidative Stress.

Diabetes is characterized by high glucose (HG) levels in the blood circulation, leading to exposure of the vascular endothelium to HG conditions. Hyperglycemia causes oxidative stress via excessive reactive oxygen species (ROS) production in the endothelium, which leads to cellular dysfunction and the development of diabetic vascular diseases. Substance-P (SP) is an endogenous peptide involved in cell proliferation and migration by activating survival-related signaling pathways.

Substance P ameliorates TNF-α-mediated impairment of human aortic vascular cells in vitro.

Vascular diseases are caused by endothelial dysfunction due to inflammation. On endothelial injury, the expression of extracellular matrix (ECM) is enhanced and nitric oxide (NO) bioavailability becomes deficient. This condition affects endothelial metabolism and leads to vascular destruction.

Substance P blocks ovariectomy-induced bone loss by modulating inflammation and potentiating stem cell function.

Osteoporosis is an age-related disease caused by imbalanced bone remodeling resulting from excessive bone resorption. Osteoporosis is tightly linked with induction of chronic inflammation, which activates osteoclasts and impairs osteoprogenitor in bone marrow. T helper 17 (Th17) cells have been recently recognized as one of major inducers in the pathophysiology of bone loss by secreting IL-17.

Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress.

Oxidative stress induces cellular damage, which accelerates aging and promotes the development of serious illnesses. Adipose-derived stem cells (ADSCs) are novel cellular therapeutic tools and have been applied for tissue regeneration. However, ADSCs from aged and diseased individuals may be affected in vivo by the accumulation of free radicals, which can impair their therapeutic efficacy.

Osteoporotic Conditions Influence the Activity of Adipose-Derived Stem Cells.

Background: Estrogen deficiency decreases bone density and increases the risk of osteoporosis and fracture, thereby necessitating reconstruction of bone regeneration. As bone marrow mesenchymal stem cell (BMSCs) lose viability and differentiation potential under osteoporotic conditions, it is impossible to use autologous BMSCs for osteoporosis treatment. As an alternative, adipose-derived stem cells (ADSCs) may serve as the source of therapeutic cells.

Substance P blocks β-aminopropionitrile-induced aortic injury through modulation of M2 monocyte-skewed monocytopoiesis.

Aortic injuries, including aortic aneurysms and dissections, are fatal vascular diseases with distinct histopathological features in the aortic tissue such as inflammation-induced endothelial dysfunction, infiltration of immune cells, and breakdown of the extracellular matrix. Few treatments are available for treating aortic aneurysms and dissections; thus, basic and clinical studies worldwide have been attempted to inhibit disease progression. Substance P (SP) exerts anti-inflammatory effects and promotes restoration of the damaged endothelium, leading to vasculature protection and facilitation of tissue repair.

Substance P accelerates wound repair by promoting neovascularization and preventing inflammation in an ischemia mouse model.

Aims: Arterial insufficiency ulcers are frequent complications of peripheral artery disease and infection or long-term neglect of the ulcer can eventually lead to amputation of the affected body part. An ischemic environment, caused by interrupted blood flow, affects the supply of nutrients and elongates the inflammation period, inducing tissue degeneration. Thus, the modulation of neovascularization and inflammation could be an ideal therapeutic strategy for ischemic wound healing.

Substance P Promotes Liver Sinusoidal Endothelium-Mediated Hepatic Regeneration by NO/HGF Regulation.

Liver sinusoidal endothelial cells (LSECs) are highly specialized and involved in hepatic regeneration by interacting with hepatic stellate cells (HSCs) and hepatocytes in a paracrine manner. However, hepatic injury can impair cellular activity and lead to endothelial dysfunction, eventually inducing the development of critical hepatic disease, including cirrhosis. Because LSECs exert their effects through paracrine factors, maintenance of paracrine potentials and survival activity in LSECs under injury stress is a critical strategy for inhibiting disease progression.

Substance P ameliorates tumor necrosis factor-alpha-induced endothelial cell dysfunction by regulating eNOS expression in vitro.

Objective: The aim of this study was to explore the beneficial effects of SP on NO production and inflammation-induced vascular endothelium cell death.

Methods: To mimic the inflammatory environment, TNF-α was treated with HUVECs, and SP was added prior to TNF-α to determine its protective effect. WST-1 assay was performed to detect cell viability.

Substance P enhances proliferation and paracrine potential of adipose-derived stem cells in vitro.

Stem cells have tremendous promise to treat intractable diseases. Notably, adipose-derived stem cells (ADSCs) are actively being investigated because of ease of sampling and high repopulation capacity in vitro. ADSCs can exert a therapeutic effect through differentiation and paracrine potential, and these actions have been proven in many diseases, including cutaneous and inflammatory diseases.