Orthopedic (Osteoarthritis & Injuries)

Mesenchymal stem cells (MSCs) are self-renewing, multi-potent, 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. This attribute repairs the subchondral bone without any loss of articular cartilage at the surface. MSCs have shown to therapeutically alter the progression of OA by down-modulating 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. Additionally, there has been significant improvement in joint function through pain reduction and increase of cartilage in the affected joint.

Diabetes

Mesenchymal Stem Cells (MSCs) found in several bodily tissues, such as bone marrow and adipose tissue, have the capacity 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 destroyed by the immune system. Mesenchymal stem cell implantation has shown an increase in insulin secretion and an increase in the number of islet cells in the pancreas. Some studies have also shown the ability of human derived mesenchymal stem cells to differentiate into B-cells which expressed the insulin gene, therefore having the ability to reverse diabetes mellitus. Furthermore, mesenchymal stem cells have been shown to travel to the sight of injury, in this case in pancreatic islets and the liver where they may have contributed to tissue repair and remodeling, as well as improving metabolic function. Diabetes type 2 studies have shown a reduction of glucose levels in the blood when stem cell therapy was done.

Chronic Obstructive Pulmonary Disease (COPD)

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 potentially suppress auto-reactive T-cells, inhibit macrophage activation, and autoimmune response, improving 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.

Degenerative Disc Disease

Adipose derived stem cell therapy uses Mesenchymal Stem Cells (MSCs) to significantly display long-term proliferation, efficient self-renewal, and multi-potent differentiation. Meaning the MSCs have the ability to end and reverse degeneration of spinal discs. More specifically through increasing disc height by 23.6%, disc water content, and gene expression. One of the main biological functions of MSCs is their ability to reproduce cartilage and bone tissue cells (multi-potent 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.

Multiple Sclerosis (MS)

MS has been explained as a chronic autoimmune disease where the immune cells attack the myelin sheath in 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 have the function to create the myelin sheath around the axons. Studies have shown that demyelination was improved after the transplantation of adipose derived stem cells, suggesting that stem cell therapy is a potential treatment for MS patients. Besides improving the demyelination of the nerve cells, and having immunomodulatory and anti-inflammatory properties, Ghasemi group also observed a recovery in locomotion function. Preclinical trials have also observed the migration of mesenchymal stem cells into the inflamed central nervous system (CNS) and induce the production of neuroprotective agents which help preserve the axons in the CNS.

Amyotrophic Lateral Sclerosis (ALS)

ALS, also known as Lou Gehrig’s disease, is involved in the degeneration of motor neurons in the primary motor cortex, the brain stem, 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 Treg cells and anti-anti-inflammatory cytokines, potentially slowing down the progression of ALS. Furthermore, other studies have demonstrated the modulation of motor neuronal 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 toxin 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.

Congestive Heart Failure

Mesenchymal stem cells possess vast therapeutic capacities and have shown potential in the treatment of heart failure in pre-clinical and some clinical settings. Pluripotent mesenchymal stem cells (MSCs) differentiate into a variety of cells, including cardiomyocytes and vascular endothelial 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.

Kidney 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 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 renoprotective.

Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenrative disease which is characterized by the loss and degeneration of dopaminergic neurons (neurons involved in the secretion of dopamine). Mesenchymal stem cells, besides showing migration to the site of injury and having immunomodulatory and anti-inflammatory properties, have shown in 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, gait, and freezing episodes. Additionally, the transplantation of adipose derived stem cells has shown an improvement in behaviors such as tremor and motility.

Rheumatoid Arthritis (RA)

Adipose derived stem cells have the potential to repair cartilage and joint tissue. Mesenchymal stem cells release immunosuppressive factors which help alleviate and avoid further progression of the disease. Besides having immune modulatory abilities, mesenchymal stem cell therapy allows for tissue repair on damaged caused by chronic inflammation. Mesenchymal stem cells also induce the production of T regulatory cells, immune cells, which are responsible to abolish autoimmune diseases. Recent studies suggest that patients achieve stable remission after stem cell treatment, due to the ‘resetting’ of the immune system.

Scleroderma

Adipose derived stem cell therapy uses Mesenchymal Stem Cells to improve skin elasticity and recovery of some functions severely impaired by this disease. Mesenchymal stem cells exhibit anti-proliferative and anti-inflammatory properties, therefore resetting of the immune system and improving the condition and slowing the progression of such disease. T-cells have shown rejuvenation having an increase surface expression of CD69 and restoring the regulatory function, causing the disease to fall in remission after treatment. The therapeutic benefit is due to mesenchymal stem cells locating the site of inflammation and releasing cytokines and growth factors that result in local anti-inflammatory effects.

Spinal Cord Injuries

Studies have shown that the transplantation of mesenchymal stem cells (MSCs) support spinal cord repair due to its self-renewing and multipotential nature. MSCs can differentiate into distinct cell lineages and have been known to give rise to neural-like cells (neurons and glial). Transplanted stem cells promote neural regeneration and rescue impaired neural function after SCI by parasecreting permissive neurotrophic molecules at the lesion site to enhance the regenerative capacity thereby providing a scaffold for the regeneration of axons and replacing lost neurons and neural cells. Adipose derived mesenchymal cells inhibit H2O2-mediated apoptosis in spinal cord-derived neural progenitor cells, improving cell survival. Through the use of these MSCs, the goal of regeneration of axons, prevention of apoptosis, replacement of lost cells in order to facilitate remylination becomes a realistic accomplishment.

Stroke

Adipose derived stem cell therapy uses Mesenchymal Stem Cells (MSCs) to significantly improve functional recovery and increase the levels of brain protection. The use of MSCs is appealing in that they allow for immune reactions to be avoided 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.

Traumatic Brain Injury

Mesenchymal Stem Cells (MSCs) found in several bodily 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. Stem cell therapy studies have shown an increase in the anti-inflammatory cytokine production, which helps preserve the blood brain barrier. Additionally, studies have also revealed localization of MSCs in the region of injury, after intravenous administration of cells that can increase levels 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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