IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease.

Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease.

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy.

Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease.

Therapy With Mesenchymal Stem Cells in Parkinson Disease: History and Perspectives.

Background: Parkinson disease (PD) is a neurodegenerative disorder affecting the basal nuclei, causing motor and cognitive disorders. Bearing in mind that standard treatments are ineffective in delaying the disease progression, alternative treatments capable of eliminating symptoms and reversing the clinical condition have been sought. Possible alternative treatments include cell therapy, especially with the use of mesenchymal stem cells (MSC).

Eicosapentaenoic Acid Enhances the Effects of Mesenchymal Stromal Cell Therapy in Experimental Allergic Asthma.

Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited.

Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation.

Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs), through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM) was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL).

Strategies to improve the therapeutic effects of mesenchymal stromal cells in respiratory diseases.

Due to their anti-inflammatory, antiapoptotic, antimicrobial, and antifibrotic properties, mesenchymal stromal cells (MSCs) have been considered a promising alternative for treatment of respiratory diseases. Nevertheless, even though MSC administration has been demonstrated to be safe in clinical trials, to date, few studies have shown evidence of MSC efficacy in respiratory diseases. The present review describes strategies to enhance the beneficial effects of MSCs, including preconditioning (under hypoxia, oxidative stress, heat shock, serum deprivation, and exposure to inflammatory biological samples) and genetic manipulation.

Skin wound healing in humans and mice: Challenges in translational research.

Despite the great progress in translational research concerning skin wound healing in the last few decades, no animal model fully predicts all clinical outcomes. The mouse is the most commonly used model, as it is easy to maintain and standardize, and is economically accessible. However, differences between murine and human skin repair, such as the contraction promoted by panniculus carnosus and the role of specific niches of skin stem cells, make it difficult to bridge the gap between preclinical and clinical studies.

Ghrelin therapy improves lung and cardiovascular function in experimental emphysema.

Background: Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance.

Mesenchymal stromal cell therapy in COPD: from bench to bedside.

COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality. The major risk factor for COPD development is cigarette smoke, and the most efficient treatment for COPD is smoking cessation. However, even after smoking cessation, inflammation, apoptosis, and oxidative stress may persist and continue contributing to disease progression.

Stem-cell extracellular vesicles and lung repair.

Four out of the ten leading causes of morbidity and mortality worldwide are lung diseases. Despite advances in comprehending the pathophysiological mechanisms involved in these disorders, for several respiratory diseases, there is still no effective treatment able to stop their natural history or reverse the morphological and functional damage they cause. In this context, recent research has supported a potential role of cell therapy for lung diseases and critical illness.

Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem cells, tumor cells and mesenchymal stem cells.

The tumor microenvironment comprises a heterogeneous population of tumorigenic and non-tumorigenic cells. Cancer stem cells (CSCs) and mesenchymal stem cells (MSCs) are components of this microenvironment and have been described as key regulators of different aspects of tumor physiology. They act differently on the tumor: CSCs are described as tumor initiators and are associated with tumor growth, drug resistance and metastasis; MSCs can integrate the tumor microenvironment after recruitment and interact with cancer cells to promote tumor modifications.

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension.

Background: Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH.

Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy.

Unlabelled: Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease.

Aims: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy.

Main Methods: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring.

Generation and characterization of transgenic mouse mesenchymal stem cell lines expressing hIGF-1 or hG-CSF.

Mesenchymal stem cells (MSC) are promising tools in the fields of cell therapy and regenerative medicine. In addition to their differentiation potential, MSC have the ability to secrete bioactive molecules that stimulate tissue regeneration. Thus, the overexpression of cytokines and growth factors may enhance the therapeutic effects of MSC.

Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

Background: Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity.

Methods: After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle.

Image-guided percutaneous intralesional administration of mesenchymal stromal cells in subjects with chronic complete spinal cord injury: a pilot study.

Background Aims: The potential of cell therapies to improve neurological function in subjects with spinal cord injury (SCI) is currently under investigation. In this context, the choice of cell type, dose, route and administration regimen are key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded and are suitable for autologous transplantation.

Luminal ANG II is internalized as a complex with ATR/ATR heterodimers to target endoplasmic reticulum in LLC-PK cells.

ANG II has many biological effects in renal physiology, particularly in Ca handling in the regulation of fluid and solute reabsorption. It involves the systemic endocrine renin-angiotensin system (RAS), but tissue and intracrine ANG II are also known. We have shown that ANG II induces heterodimerization of its AT and AT receptors (ATR and ATR) to stimulate sarco(endo)plasmic reticulum Ca-ATPase (SERCA) activity.

Controlled invasive mechanical ventilation strategies in obese patients undergoing surgery.

The obesity prevalence is increasing in surgical population. As the number of obese surgical patients increases, so does the demand for mechanical ventilation. Nevertheless, ventilatory strategies in this population are challenging, since obesity results in pathophysiological changes in respiratory function.

Long-term effect of a chronic low-protein multideficient diet on the heart: Hypertension and heart failure in chronically malnourished young adult rats.

Background: We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure.

Methods And Results: Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats.

Cardiosphere-derived cells do not improve cardiac function in rats with cardiac failure.

Background: Heart failure represents an important public health issue due to its high costs and growing incidence worldwide. Evidence showing the regenerative potential of postmitotic heart tissue has suggested the existence of endogenous cardiac stem cells in adult hearts. Cardiosphere-derived cells (CDC) constitute a candidate pool of such cardiac stem cells.