Human Adipose-Derived Mesenchymal Stem Cells Reduce Inflammation

February 26, 2015

Human Adipose-Derived Mesenchymal Stem Cells Reduce Inflammation modulates Regulatory T Cells in Rheumatoid Arthritis

Mesenchymal stem cells are a rare type of cells that are multi-potent and can be isolated from the adipose tissues, bone marrow among other crucial sources. These cells have very unique properties that have seen them become targets of very many medical therapies especially in treating degenerative diseases like aging and even joint diseases like arthritis. These cells have been found to be also very effective in modulating the functions of immune cells, including T cells, B cells, natural killer cells, monocyte or macrophages, dendritic cells, and neutrophils. T cells, activated to perform a range of different effector functions, are the primary mediators of many autoimmune and inflammatory diseases as well as of transplant rejection and graft-versus-host disease. Some of the well-defined T-Cell effector cells include; CD4+ (T helper cell) subsets Th1, Th2, and Th17 cells and cytotoxic T lymphocytes which are derived from antigen-specific activation of simple CD8+ precursors. In addition, naturally occurring and induced regulatory T cells represent CD4+ and CD8+ T-cell phenotypes that potently suppress effector T cells to prevent autoimmunity, maintain self-tolerance, and limit inflammatory tissue injury. The ability of adipose-derived mesenchymal stem cells to suppress the effector T-Cells and limit inflammation has made them very effective in treating rheumatoid arthritis which is characterized with inflammations around the joints. Typically, many immune-mediated diseases entail an imbalance between regulatory T cells and effector T cells of one or more phenotypes. Mesenchymal Stem Cells broadly suppress T-cell activation and proliferation in a controlled environment outside of a living organism via (Vitro) a plethora of soluble and cell contact-dependent mediators. These mediators may work in two ways; first they can work directly on T cells or indirectly via modulation of antigen-presenting cells and other accessory cells. Mesenchymal Stem Cells administration has also been shown to be variably associated with beneficial effects in autoimmune and transplant models as well as in several human clinical trials. However, in a small number of studies Mesenchymal Stem Cells administration has been found to heighten T cell-mediated tissue injury. The multiple effects of Mesenchymal Stem Cells on cellular immunity may reflect their diverse influences on the different T-cell effector subpopulations and their capacity to specifically protect or induce regulatory T-cell populations.

Mesenchymal Stem Cells

Mesenchymal stem cell modulation of T cell-mediated immune responses

To repeat for emphasis, the T cells are the primary cellular effectors of the adaptive immune system and their functional properties are central to antigen specificity and memory associated with cognate immunity, this therefore means that to a greater extent they are responsible for rejection of implanted cells of varied specificity. Antigen-specific activation and differentiation of naïve T cells result in the generation of a range of T-cell phenotypes that may be defined by the acquisition of characteristic cytokine secretion profiles, cytolytic mechanisms, or counter-regulatory properties.

Following antigen-specific adaptive immune responses, a small proportion of activated T cells persist as memory cells and have the capacity to respond more rapidly and potently to secondary encounters with the same antigen. These memory cells may retain the effector phenotype imprinted upon them during primary activation. When these memory cells are appropriately coordinated and regulated, the diversity of T-cell effector phenotypes allows immune protection against a multitude of pathogenic microorganisms while maintaining self-tolerance and homeostasis. On the other hand, over exuberant pro-inflammatory T-cell responses may lead to auto-immune and allergic diseases, including multiple sclerosis, inflammatory bowel disease, type 1 diabetes mellitus, and asthma. Therefore it is crucial to have a modulatory strategy on the effector T-cells. Furthermore, life-saving treatments such as allogeneic bone marrow and solid organ transplantation may be complicated by alloantigen-specific T-cell immune responses, resulting in graft-versus-host disease (GvHD) or transplant rejection.

Study finding

Mesenchymal Stem Cells and Inflammation In a research study done at School of Medicine, University of Seville, Seville, Spain by Gonzalez-Rey E, Gonzalez MA, Varela N, O’Valle F, Hernandez-Cortes P, Rico L, Büscher D, and Delgado M it was found that human adipose-derived mesenchymal stem cells suppressed the antigen-specific response of T cells from patients with rheumatoid arthritis. Human adipose-derived mesenchymal stem cells inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. On the contrary, the numbers of IL10-producing T cells and monocytes were significantly augmented upon human adipose stem cell treatment. The suppressive activity of human adipose-derived mesenchymal stem cells was cell-to-cell contact dependent and independent. Human adipose-derived mesenchymal stem cells also stimulated the generation of FoxP3 protein-expressing CD4 (+) CD25 (+) regulatory T cells, with the capacity to suppress collagen-specific T cell responses. Lastly, human adipose-derived mesenchymal stem cells down regulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from patients with rheumatoid arthritis.

The study had sought to find out the immunosuppressive activity of human adipose-derived mesenchymal stem cells on collagen-reactive T cells from patients with rheumatoid arthritis. The method used involved investigating the effects of human adipose-derived mesenchymal stem cells on collagen-reactive RA human T cell proliferation and cytokine production as well as effects on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from patients with rheumatoid arthritis. Stem cell therapy is a promising approach to treatment of degenerative diseases like arthritis but still you will need an expert in degenerative medicine. Dr. Dalal Akoury (MD) an expert in integrative and regenerative medicine will be able to help. Visit us at AWAREmed Health and Wellness Resource Centre at Myrtle Beach, South Carolina

Human Adipose-Derived Mesenchymal Stem Cells Reduce Inflammation modulates Regulatory T Cells in Rheumatoid Arthritis

Histamine, Metabolism, Neuro-excitatory and Neurotransmitters

February 10, 2015

Role of Histamine, Metabolism, Neuro-excitatory and Neurotransmitters for Addiction

Histamine refers to transmitter that is endogenous in nature and one that is involved in gastric secretions, allergic manifestations and vigilance regulation. It is found in tissues of all animals especially mamma also with high concentrations in the skin, liver and lungs. In the tissues, the transmitter histamine occurs in mast cells which are simply a group of cells whose cytoplasm has high concentrations of basophilic granulations.

In the mast cells histamine exists bonded to acidic compounds like heparin. In most cells with histamine, its production is slow and when it sis depleted t may take several weeks to go back to normal levels. The brain also contains histamine in certain level. Histamine occurs in the brain region in the hypothalamus based o circadian rhythm which occurs in the brain. Its concentration in the plasma does not exceed 1 microgram per liter but this concentration is high in patients suffering from asthma.

neurotransmitters

In the blood the level of histamine ranges from 10 to 100 micrograms in a liter and is primarily concentrated in the basophils. This concentration as studies show rises especially in patients suffering from medical conditions like gastrodudenal ulcers and chronic myelogenous leukemia. Histamine depreciates some times in the body. This means that more has to be produced to replace the one that is lost. This replacement is often slow and can take several weeks. However, histamine renewal in the nervous system and the gastric cells is at faster rate because it is released continuously.

Histamine and Metabolism

Naturally the distribution of histamine in the body is not usually uniform. It however, occurs in in higher concentrations in the mucosa of the gastric system. Its metabolism is dependent on enzymes such as diamine oxidase, histamine N-methyltransferase and histidine decarboxylase. These enzymes seem to be dominant in the stomach region. Studies have been carried out to determine exactly the concentration of histamine in the gastric system. For years this has been a subject of controversial debate and it was only recently that a solution was found. Studies show that the inactivation process of histamine by histamine methyltrasferase takes place in the gastric mucosa that has a significant activity of enzymes.

However it is worthwhile to note that the intestines, liver and spleen have much higher activities which points towards little specification of catabolism of histamine in the gastric mucosa. There have also been debates concerning the activity of diamine oxidase which for years was thought not to exist in the corpus mucosa. Recent studies however, show that moderate enzyme activities of this enzyme is present in some species among them man. In this case then, the metabolism of histamine n the gastric mucosa does not mean its existence in mammalian tissues. Activities of these enzymes could also act as an indication that it has significant physiological functions in the body.

The formation and inactivation of histamine has been shown to be regulated through enzyme activities by during the process of secreting acid. Histamine N-methyltrasferase and histidine decarboxylase are enhanced by gastrin activities and not necessarily influenced by vagal stimulation.

Neuro excitatory and Neurotransmitters for Addiction

Studies show that rugs especially alcohol affect to a great extent the brain as well as some physical processes of the body. There are several reasons that make a person an alcohol addict. These reasons may range from depression, stress, impulse of just mere pleasure. Once a person becomes alcohol dependent, a pattern has already been established and this affects the neural system of the person.

Histamine

The Neurotransmitter Process

In order to fully understand the neurological effects of alcohol addiction in the brain, there is need to understand how the brain transmitters work. The brain communicates through neurons that send messages form ne cells of the brain to an0ther. Transmission of nerve signals takes place from one brain region to another. Once a neuron has been activated, an electrical signal is produced which travels all through the membrane that surrounds the body and axon of the neuron. The signal reaches the end of the neuron and this triggers neurotransmitters to be released from the brain cells. The neurotransmitters then travel from one neuron to another. On reaching the other neuron, the molecules in the transmitter bind with receptors in the neuron and this triggers new electric signal to be produced. Production of new signals depends on the type of neurotransmitter that is involved in the process.

Most neurotransmitters exhibit inhibitory and excitatory effects. This is dependent on the region of the brain and the receptors present in that region. Neurotransmitters with excitatory effects include among others glutamate, dopamine and serotonin while those with inhibitory effects include gamma-aminobutyric acid most commonly referred to as GABA. When one takes alcohol it tends to reinforce the transmitter system. This affects many neural transmitter processes which trigger some long term effects like withdrawal, tolerance, dependence, sensitization and finally addiction.

This information can be found for free at www.awaremednetwork.com. Here you will also find other health and awareness tips.

Role of Histamine, Metabolism, Neuro-excitatory and Neurotransmitters for Addiction

Phytomedicine In Cancer Treatment

August 12, 2014

Phytomedicine and DIM Can Effectively Be Used In Triple Negative Breast Cancer Treatment

Phytomedicine refers to the application of scientific research and the highest standards of professionalism to the herbal medicine practice. The use of phytomedicine is not new though. It has been in practice for quite a long time in fact the name phytomedicine is derived from the word used in other parts of Europe, where plant based medicines are provided by doctors and pharmacists as ‘phytomedicine’ to their patients. Phytomedicine is more advanced in herbal medicine as it involves scientific research to ascertain the potency of the natures given herbals before they are prescribed to be used by any patient. The doctors who use phytomedicine are called phytotherapists and they treat their patients with the best herbs that fit their king of diseases. Phytotherapists choose the best herbs from the most effective herbs ensuring that very patient get the best combination of the phytomedicine.

Phytomedicine is practiced in clinical treatment of diseases in most parts of the world and is a growing field as it involves scientific research and information on the use of plant medicinal components and their safety in use. There are methods that are used to evaluate the effectiveness of plant medicines which are similar to the evaluation of orthodox medicine. Herbs unlike the orthodox medicine that focus on given chemicals contain very many bioactive components. The phytomedicine may involve use of a combination of herbs to come up with a therapy that will heal the body and strengthen its immune system to fight diseases better.

Phytomedicine are safe for use for many diseases and cancer is no exception. After very many clinical trials of phytomedicine the use of phytomedicine in treatment of various conditions have been recognized in most countries through the world. Section 12 (1) of the 1968 Medicines Act permits Phytotherapists to make and dispense herbal remedies to individual patients following a consultation.

As used in cancer treatment, Phytomedicine involves selection of plant medicines to stimulate or strengthen the body’s own functions and immune system, hence support the body to heal itself. The phytotherapist knows that each cancer patient is a unique individual and hence diagnoses and assesses the needs of the cancer patient uniquely. The patient will thereafter be given a prescription of combined plant products that work best in healing them.

Some of the natural plants components that have been used in phytomedicine to treat cancer include; resveratrol, saponins, silymarin, curcumin, peach compounds, green tea extracts, coffee enemas and grape seed extracts. These phytomedicine are rich in anticancer properties and are even safer for use in cancer treatment. The use of chemotherapy in cancer treatment may fail to work and if chemotherapy is done repeatedly the tumors only become more resistant to the drugs that are supposed to be killing them. The scientists have found out that the use of natural products work better in cancer treatments as they target multiple pathways thereby inhibiting growth and spread of the cancer cells in the body. Some of this phytomedicine help in killing cancer cell by inducing apoptosis in tumors.

EGCG and GSE are two popular plant extracts that have attracted much attention in recent years due to their antioxidant, antimicrobial, anticarcinogenic, and anti-inflammatory properties.

Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is the most difficult cancer to treat as these cancer cells are very resistant to drugs. These cancer cells do not have the characteristic receptors for estrogen, progesterone and Her2/neu. This makes it very hard to treat a patient with Triple negative breast cancer (TNBC) as most treatments especially the conventional cancer treatments target these receptors that are missing in the cells. Without these receptors such treatments do not work. For instance, Tamoxifen targets estrogen receptors, in absence of estrogen receptors Tamoxifen cannot work in cancer treatment. For this reason, TNBC is considered the most aggressive, the most likely to be treated with less-targeted (and therefore more toxic) forms of chemotherapy, and the soonest to return when treatment fails. For Triple negative breast cancer (TNBC) target therapies are not the best options for treatment.

Today it is approximated that between 15-25% of all breast cancer cases are triple negative. Being that the conventional cancer treatments cannot be used in treatment of Triple negative breast cancer it is important to seek effective treatment through other means. Phytomedicine can effectively be used in treatment of Triple negative breast cancer (TNBC) as it works better here than any other target therapies.

DIM

Recent research has shown that diindolylmethane (DIM) promotes production of beneficial interferon gamma by breast cancer cells. With reference to scientists at the University of California, Berkeley, the anticancer effect of DIM is evident as the interferon gamma is known to play an important role in inhibiting the development of primary tumors. It has also been proven that DIM increases cellular stress response pathways in breast, prostate and cervical cancer cells. The increase of cellular stress increases the vulnerability of cancer cells to destruction. Studies have shown that DIM induces apoptosis in both breast and prostate cancer cells.

Phytomedicine According to a study done by Scientists at Wayne State University School of Medicine, DIM affects the functions of genes that control carcinogenesis, cell survival, and physiologic behaviors. It also inhibits the growth of new blood vessels that are necessary for spread and growth of tumors. In a the study that was conducted by University of California, Berkeley it was found that DIM inhibited angiogenesis on both cultures assays as well as animal models. It is therefore effective and can be used in treatment of Triple negative breast cancer (TNBC).

Dr. Dalal Akoury (MD) is an experienced integrative cancer doctor that has helped many cancer patients in their fight against the disease. She has worked hard not only in treating the disease but also in availing informational support to cancer patients at Awaremed which has become a place called home for many cancer patients. Call on her now and get help on cancer.

Phytomedicine and DIM Can Effectively Be Used In Triple Negative Breast Cancer Treatment

Tag Archives: Proceedings of the National Academy of Sciences of the United States of America