User:Sunstarrrr/Clinical uses of mesenchymal stem cells

Task: find definitions for the two terms highlighted in red

new article: systemic infusion: administering something to the entire body instead of a localized area. Infusion is a method of administering fluids like drugs into the circulatory system. Systemic is relating to an entire system instead of just one part.

- bioactive agents: (bioactive compounds) substances that can influence an organism, tissue or cell. Examples include enzymes, drugs, and vitamins.

- revise phrasing of the article to make it more accessible to the general public

- add a section of disadvantages/possible safety concerns

potential sources: https://www.sciencedirect.com/science/article/pii/S018844092030638X

Article Draft [copied from the article Clinical Uses of Mesenchymal Stem Cells]
Adult mesenchymal stem cells (MSCs) are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.

Source of MSCs
In the research process of expanding the therapeutic uses of MSCs, they are grown in laboratories or grown using medication to stimulate new cell growth within the human body. In MSC therapy, most of the cells are extracted from the adult patient’s bone marrow

Preparation of MSCs
MSCs can be obtained via a procedure called bone marrow aspiration. A needle is inserted into the back of the patients hip bone and cells are removed to be grown under controlled in vitro conditions in a lab. Over a course of two or three weeks, the cells will multiply and differentiate into specialized cells. The number of fully differentiated cells and their phenotype can be influenced in three ways. The first one is by varying the initial seed density in the culture medium. The second is by changing the conditions of the medium. The third is by the addition of additives such as proteins or growth hormones to the culture medium to promote growth. The mature cells are then harvested and injected back into the patient through local delivery or systemic infusion.

Culturing and Isolation of MSCs
Isolation of MSCs from the bone marrow requires an invasive procedure. MSCs can also be isolated from birth-associated tissues such as the umbilical cord without the need for an invasive surgical procedure. Differences in isolation efficiency are attributed to the availability, condition, and age of the donor tissue. An issue related to culturing MSCs is the insufficient number of cells that can be produced. During long-term culture, MSCs age, lose their ability to differentiate, and have a higher chance to undergo malignant transformation.

Human mesenchymal stem cells (hMSCs)

- Can include a table of the Distribution of clinical trials registered at clinicaltrial.gov by the medical field

An Alternative to Embryonic Stem Cells [copied from the article Clinical Uses of Mesenchymal Stem Cells]
Several different forms of stem cells have been identified and studied in the field of regenerative medicine. One of the most extensively studied stem cell types are embryonic stem cells (ESCs). ESCs possess many of the same therapeutic properties as MSCs, including the ability to self-regenerate and differentiate into a number of specialized cells. Their therapeutic abilities have been demonstrated in a number of studies of autoimmunity and neurodegeneration in animal models.

However, their therapeutic potential has been largely limited by several key factors. Injected ESCs have been shown to increase the risk for tumor formation in the host patient. Also, the host’s immune system may reject injected ESCs and thus eliminate their therapeutic effects1. Finally, research has been largely limited due to the ethical issues that surround their controversial procurement from fertilized embryos.

Safety of Mesenchymal Stem Cells
Human mesenchymal stem cell therapy is limited due to variation in individual response to treatment and the high number of cells needed for treatment. More long-term studies are needed to ensure the safety of MSCs. In previous studies that observed the safety of clinical MSC use, no serious side effects were noted. However, there has been some cases where there was both improvement and toxicity inflicted on the targeted organ, as well as cases where treatment of MSCs did not show improvement of function at all. In addition, there is a risk of tumorigenesis after stem cell transplantation due to the ability of stem cells to proliferate and resist apoptosis. Genetic mutations in stem cells as well as conditions at target tissue may result in formation of a cancerous tumor. Studies have shown that BM-MSCs can migrate to solid tumors and promote tumor growth in various cancer models   through the secretion of proangiogenic factors.

Therapeutic Mechanisms (copied from original article)
Mesenchymal stem cells have been used to treat a variety of disorders including cardiovascular diseases, spinal cord injury, bone and cartilage repair, and autoimmune diseases.

The exact therapeutic mechanisms of mesenchymal stem cells in the treatment of multiple sclerosis are still very much up to debate among stem cell researchers. Some of the suggested mechanisms are immunomodulation, neuroprotection, and neuroregeneration.

Immunomodulation


 * Mesenchymal stem cells exhibit immunmodulatory properties through the release of bioactive agents such as cytokines that can inhibit autoimmune responses. In patients with multiple sclerosis, autoreactive lymphocytes such as T and B cells cause damage to the centrla nervous system by attacking myelin proteins. Myelin proteins make up the myelin sheath that functions in protecting nerve axons, maintaining structural integrity, and enabling the efficient transmission of nerve impulses. By suppressing the unregulated proliferation of T and B cells, mesenchymal stem cells can potentially minimize and control on-going damage to the central nervous system.


 * Mesenchymal stem cells can also produce an immunomodulating effect by stimulating the maturation of antigen presenting cells. Antigen presenting cells trigger the immune system to produce antibodies that can destroy potentially harmful material. This property allows mesenchymal stem cells to actively contribute to neutralizing harmful autoreactive by-products of multiple sclerosis.

Neuroprotection


 * Mesenchymal stem cells can promote neuroprotection in the central nervous systems of patients with multiple sclerosis which may prevent the progression of the disease to chronic disability. Mesenchymal stem cells contribute to neuroprotection through several different mechanisms. These mechanisms include inhibiting apoptosis which will prevent the death of healthy cells and prevent gliosis which will prevent the formation of a glial scar. They can also stimulate local progenitor cells to produce replacement cells that can assist in rebuilding the myelin sheath.

Neuroregeneration


 * The regenerative abilities of the central nervous system are greatly decreased in adults, impairing its ability to regenerate axons following injury. In addition to this natural limitation, patients with multiple sclerosis exhibit even greater decreases in neuroregeneration coinciding with increases in neurodegeneration. In particular, patients with multiple sclerosis experience a significant decrease in the number of neural stem cells which are responsible for producing large numbers of progenitor cells that are necessary for normal maintenance and function. Decreases in the neural stem cells results in severe damage to the ability of the central nervous system to repair itself. This process results in the amplified neurodegeneration exhibited in patients with multiple sclerosis.


 * Mesenchymal stem cells have the ability to stimulate neuroregeneration by contributing to cell replacement through differentiating into neural stem cells in response to inflammation. The neural stem cells can then promote the repair of damaged axons and create replacement cells for the damaged tissue.


 * Regeneration and repair of damaged axons has been shown to occur naturally and spontaneously in the central nervous system. This shows that it is an environment capable of unassisted, natural healing. naturally possesses an environment that is susceptible to regeneration. Mesenchymal stem cells contribute to this regenerative environment by releasing bioactive agents that inhibit apoptosis and thus create an ideal regenerative environment.

Multiple Sclerosis
A vast amount research has been conducted in recent years for the use of mesenchymal stem cells to treat multiple sclerosis. This form of treatment for the disease has been tested in many studies of experimental allergic encephalomyelitis, the animal model of multiple sclerosis, and several published and on-going phase I and phase II human trials.



Cardiovascular Diseases
Mesenchymal stem cells are able to alleviate heart fiber injury and prevent cardiac muscle cell death in mouse models of myocardial infarction, or heart attack, and prevent its further development. They can migrate to areas of inflammation and decrease infarction and improve cardiac function.

Brain Disorders
Mesenchymal stem cells have the potential to treat brain strokes as well. They can secrete factors that stimulate the function of brain cells, leading to neuron formation, blood vessel formation, and improved synaptic plasticity. They can also differentiate into neurons and neural cells to replace damaged cells. Behavioral tests performed in mouse models demonstrated a return back to normal brain function after treatment with mesenchymal stem cells.

Liver Inflammation
Mesenchymal stem cells can also regenerate and repair damaged liver cells. In mouse models of liver fibrosis, mesenchymal stem cells delivered to the liver were shown to improve liver function by reducing inflammation and necrosis and inducing hepatocyte regeneration.