Clinical Research

ALS, also known as Lou Gherig’s disease, is involved in the degeneration of motor neurons in the primary motor cortex, the brainstem and spinal cord. The loss of motor neurons results in the inability to control muscle movements. Mesenchymal stem cells, found in various tissues of the body such as bone marrow and adipose tissue, can potentially differentiate into different cell types including neurons, making stem cell therapy a potential treatment for ALS patients. Recent studies have shown that regulatory T lymphocytes (responsible to modulate the immune system) are upregulated during the stable disease phase of ALS. After stem cell transplantation, studies have shown that stem cells induce the production of T regulatory cells and anti-inflammatory cytokines, potentially slowing down the progression of ALS. Furthermore, other studies have demonstrated the modulation of motor neuron response to cell death and inflammation. Impaired glutamate uptake function of astrocytes is associated with the accumulation of glutamate around the nerve cells in ALS patients. Glutamate is known to have a toxic effect on nerve cells, therefore leading to their death. Mesenchymal stem cells have shown to regulate the uptake of glutamate, thus decreasing the levels of glutamate around the nerve cells and decreasing cell death.

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• Transplantation of Human Adipose Derived Stem Cells Selays Clinical Onset and prolongs Life Span in ALS mouse model.

Mesenchymal stem cells possess vast therapeutic capacities and have shown potential in the treatment of heart failure in preclinical and some clinical settings. Mesenchymal stem cells (MSCs) differentiate into a variety of cells. Through the use of MSCs the following was successfully seen: the induction of myogenesis and angiogenesis; differentiation of transplanted MSCs into cardiomyocytes, vascular endothelial cells, and smooth muscle cells; secretion of large amounts of VEGF, HGF, AM, and IGF-1; improvement of cardiac function and inhibition of ventricular remodeling; and decrease in collagen volume fraction in the myocardium. The primary mechanism of action for this cell therapy is through paracrine effects that include the release of cytokines, chemokines, and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate endogenous regenerative mechanisms.

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• Stem Cell Therapy for Heart Failure
• Transplantation of Mesenchymal Stem Cells Improves Cardiac Function
• Stem Cell therapy in Patients with Heart Failure
• Clinical Practice Guidelines for Stem Cell Therapy in Cardiovascular Diseases

Patients may experience improvements in function and quality of life parameters. Recent studies have shown that adipose stem cells reduce inflammation in the airway alveoli in response to cigarette smoke exposure or other airway irritants, and also decreased lung cell death. Stem cells also have the potential to stimulate the formation of new capillaries which may lead to tissue repair and oxygen delivery. Mesenchymal stem cells have shown the ability to suppress autoreactive T-cells, inhibit macrophage activation and autoimmune response which may help to improve lung functionality in COPD patients. Improvement in lung capacity can be measured by exercise capacity. Patients’ improvements may be also monitored by the St. George Respiratory Questionnaire.

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• Using Cell-Based Strategies to Break the link between bronchopulmonary dysplasia and the development of chronic lung disease in later life
• Adipose stem cell treatment in mice attenuates lung and systemic injury
• Bone-marrow derived mesenchymal stem cell repair of injured lung
• Experimental basis and new insights for cell therapy in COPD

Mesenchymal Stem Cells (MSCs) display long-term proliferation, efficient self-renewal, and multipotent differentiation. Because of these characteristics, MSCs may have the ability to stop and reverse degeneration of spinal discs. Some studies have shown anincrease in disc height, disc water content, and gene expression. One of the main biological functions of MSCs is their ability to reproduce cartilage and bone tissue cells (multipotent differentiation capability). This is important in degenerative disc disease, since a large number of cells from the outer ring (annulus fibrosus) and the inner gelatinous (nucleus pulposus) of the discs are of a cartilaginous nature.

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• Cell Therapy for Age related Intervertebral Disc Pathologies Disc
• Stem Cells in Preclinical Spine Studies
• Treatment of Degenerative Disc Disease

Mesenchymal Stem Cells (MSCs) found in several bodily tissues, such as bone marrow and adipose tissue, have the capacity to differentiate and migrate to the site of damage and secrete growth factors or cytokines. In type 1 diabetes the insulin producing cells, B-cells within the pancreatic islets are being destructed by the immune system. Mesenchymal stem cell implantation may increase insulin secretion and increase the number of islet cells in the pancreas. Some studies have also shown the ability of MSCs to differentiate into B-cells which expressed the insulin gene, therefore having the ability to reverse diabetes mellitus. Furthermore, MSCs may travel or home to the sight of injury, in this case in pancreatic islets and the liver where they may contribute to tissue repair and remodeling, as well as improving metabolic function. According to cell therapy studies of diabetes type 2, patients have shown a reduction of glucose levels in the blood.

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• Stem Cell therapy for Type 1 Diabetes
• Stem Cells Paradigm and Present Concepts on Diabetes
• Multiple Intravenous Infusions of Bone Marrow Mesenchymal Stem Cells Reverse Hyperglycemia in type 2 Diabetes
• Acute Response of Peripheral Blood Cell to Autologous Stem Cell Transplantaion in Type 1 Diabetes
• A Concise Review: Mesenchymal Stem Cells for Diabetes

Mesenchymal Stem Cells (MSCs) found in several bodily tissues, such as bone marrow and adipose tissue, have the capacity to differentiate and migrate to the site of damage to promote structural and functional repair. In kidney disease, the nephrons which are tubular structures in the kidney, are responsible for all the functions of the kidney. These tubular structures are lined by tubular epithelial cells. The dysfunction and loss of these tubular epithelial cells play important roles in the process of kidney failure after ischemic or toxic challenge. It has been shown that mesenchymal cells migrate to the damaged kidney and differentiate into tubular epithelial cells restoring renal function and structure. Besides differentiating into epithelial cells, mesenchymal stem cells have also shown immunomodulatory capabilities and express growth factors known to be renal protective.

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• Mesenchymal Stromal Cells Promotes Solid Organ Transplantation Tolerance
• Stem Cell Therapy for Liver Disease
• MSC in renal disease and kidney function: A Review
• Mesenchymal Stem Cells as a Rescue Approach for Recovery of Deteriorating Kidney Function

MS is a chronic autoimmune disease where the immune cells attack the myelin sheath including nerve cells from the brain and spinal cord. When the nerve cells are demyelinated their function is disrupted leading to severe physical or cognitive problems. Mesenchymal stem cells, found in many tissues in the body including adipose and bone marrow, have the ability to differentiate into different types of cells such as nerve cells and oligodendrocytes. Oligodendrocytes create the myelin sheath around the axons. Studies have shown that demyelination was improved after the transplantation of stem cells, suggesting that stem cell therapy is a potential treatment for MS patients. In addition, the cells may have an immunomodulatory and anti-inflammatory effect which leads to a recovery in locomotion function. Preclinical trials have also observed the migration of mesenchymal stem cells into the inflamed central nervous system (CNS). The cells mayinduce the production of neuroprotective agents which help to preserve the axons in the CNS.

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• The Mesenchymal Stem Cells in Multiple Sclerosis
• Clinical and Pathological Effects of Intrathecal Injection of
• The Potential of Mesenchymal Stromal Cells as a Novel Cellular Therapy for Multiple Sclerosis
• Mesenchymal Stem Cells as Treatment for MS:Progress to Date.
• Safety and Immunological Effects of Mesenchymal

Mesenchymal stem cells (MSCs) are self-renewing, multipotent progenitor cells with multi-lineage potential to differentiate into cell types of mesodermal origin. Due to this attribute, MSCs can differentiate into chondrocytes, which are later replaced by bone. These cells may repair the subchondral bone without any loss of articular cartilage at the surface. MSCs have shown to therapeutically alter the progression of OA by down-regulating the release and expression of the main OA inflammatory factors and chemokines (signaling proteins secreted by cells) directly involved in the progression of the disease. According to the literature, there are reports of significant improvements in joint function, reduction in pain, and an increase of cartilage in the affected joint.

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• Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration
• Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head
• Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis
• Mesenchymal Stem Cell Therapy for knee Osteoarthritis: Preliminary report of Four Patients
• Mesenchymal stem cells for the treatment of cartilage lesions
• Knee chondral injuries:Clinical treatment strategies and experimental models
• Adipose Derived Stem Cells Current State of the Art
• Stem Cell Therapy in a Caprine Model of Osteoarthritis

Parkinson’s disease is the second most common neurodegenerative disease which is characterized by the loss and degeneration of dopaminergic neurons (neurons involved in the secretion of dopamine). Mesenchymal stem cells have the ability to migrate to sites of injury and have an immunomodulatory and anti-inflammatory properties. In addition, recent studies have shown their capacity to protect and regenerate damaged dopaminergic neurons. The production of diffusible trophic factor produced by mesenchymal stem cells supports the activation of neurogenesis as well as the integration of new neurons in a functional network. A long term-clinical study has shown improvements in symptoms such as facial expression and gait and freezing episodes. Additionally, the transplantation of stem cells has shown an improvement in behaviors such as tremor and motility.

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• Therapeutic Effects of Human Mesenchymal Stem Cells
• Human Adipose Tissue-Derived Multilineage Progenitor Cells
• The Promises of Stem Cells: Stem Cell Therapy for Movement Disorders

Stem cells have the potential to repair cartilage and joint tissue. MSCs may release immunosuppressive factors which help alleviate and avoid further progression of the disease. In addition, stem cell therapy may promote tissue repair in damaged joints caused by chronic inflammation. Mesenchymal stem cells also induce the production of T regulatory cells which may help to regulate autoimmune diseases. Recent studies suggest that some patients may achieve stable remission after stem cell treatment, due to the ‘resetting’ of the immune system.

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• Mesenchymal Stem Cell and RA
• Stem Cell Transplantation in Rheumatoid Arthritis
• Regenerative Medicine in Rheumatic Disease-Progress in Tissue Engineering
• Autologous Stromal Vascular Fraction Cells a Tool for Facilitating Tolerance in Rheumatic Disease
• Stem Cells in the Treatment of Inflammatory Arthritis

Stem Cells may help to improve skin elasticity and recovery of some functions severely impaired by scleroderma. MSCs exhibit anti-proliferative and anti-inflammatory properties, and may help to reset the immune system. This may lead to clinical improvements or slowing the progression of autoimmune diseases like scleroderma. T-cells help to regulate immune responses and may be increased with stem cell therapy which could lead to autoimmune disease remission. In addition, a therapeutic benefit at the site of inflammation may be seen due to MSCs releasing cytokines and growth factors that result in local anti-inflammatory effects.

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• Autologous adipose-derived stromal vascular fraction in patients with systemic sclerosis: 12-month follow-up
• MSCs for Scleroderma
• Adult Stem Cell Treatment of Slceroderma
• Adult Stem Cells in Treatment of Autoimmune Diseases
• Mesenchymal Stem Cell Therapy for Scleroderma

Studies have shown that the transplantation of mesenchymal stem cells (MSCs) support spinal cord repair due to their self-renewing and multi-potential nature. MSCs can differentiate into distinct cell lineages and have been known to give rise to neural-like cells. Transplanted stem cells may promote neural regeneration and rescue impaired neural function after SCI. MSCs may create a paracrine effect in which neurotrophic molecules at the lesion site enhance the regenerative capacity allowing for the regeneration of axons and replacing lost neurons and neural cells. Stem cells inhibit H2O2-mediated apoptosis in spinal cord-derived neural progenitor cells and improve cell survival.

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• MSC for Prevention and Managment of Intervertebral Disc Degeneration
• Mesenchymal Stem cells Secretome:A New Paradigm
• Regeneration Potential and Mechanism of Bone Marrow Mesenchymal
• Mesenchymal Stem Cells as an Immunomodulatory Therapeutic Strategy

Mesenchymal Stem Cells (MSCs) may improve functional recovery and increase the levels of brain protection after stroke. The use of MSCs is appealing in that they are naturally anti-inflammatory and can develop into more than one cell type (in this case, neural cells). They also secrete cytokines, growth and trophic factors, all of which are active mechanisms that lead to improved neurological functions. In addition, MSCs have also been found to reduce cell death, promote internal cellular proliferation, and normalize ischemia-induced changes after stroke.

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• A Long-Term Follow-Up Study of Intravenous Autologous
• Effects of Intravenous Administration of Allogenic Stem Cells:Ischemic Stroke
• Autologous Mesenchymal Stem Cell in Stroke Patients

Mesenchymal Stem Cells (MSCs) found in several tissues, such as bone marrow and adipose tissue, have the capacity to produce growth and trophic factors in vivo and in vitro. In TBI patients with damaged brain cells, MSCs have facilitated the production of factors that activate the internal restorative mechanisms within the injured brain. According to studies, stem cell therapy may increase the production of anti-inflammatory cytokines, which may to heal the brain tissue. Additionally, studies have also revealed localization of MSCs to the region of injury with an increase in the level of neurotrophic growth factors such as NGF, BDNF, and bFGF. These growth factors have provided neuroprotective and beneficial effects in studies with brain injury. Mesenchymal stem cells have also shown the ability to restore cerebral blood flow by inducing the formation of new blood vessels.

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• Transplanted Neural Stem Cells Survive
• Treatment of Traumatic Brain Injury in Adult Rats with Intravenous Administration of Human Bone Marrow Stromal Cells
• Neuroprotective Effects of MSC on Sensorimotor and Recovery After Brain Injury
• Stem Cells in Traumatic Brain Injury