What Are Stem Cells?
Stem cells were first isolated from mouse embryos and cultivated in the early 1980s. Since that time, scientists have accomplished the same with human stem cells, learned how to maintain their best features, and harboured aspirations to use their unique properties in regenerative medicine. Several decades earlier, human blood-forming stem cells from adults were found and described.
As defined, stem cells in human bodies can divide, replenish and mature into specialised cell types which then construct the tissues and organs. Blood stem cells, or haematopoietic stem cells (HSCs) potency is limited, as they are only capable of giving rise to blood cells. Scientists also found a way to transform and reprogramme adult cells into stem cells that can either divide or differentiate into other cell types (induced pluripotent stem cells, iPSCs).
However, there were some problems with stem cell application in clinical practice:
- As anticipated, the use of embryonic cells leads to ethical questions.
- Reprogrammed cells can divide uncontrollably, so there is a risk of malignancies.
Some scientists continued to study cells from bone marrow – the tissue where blood cells are born and mature. In the 1970s, the existence of various precursors for bone and connective tissue within the bone marrow was demonstrated. These cells were named mesenchymal stem (or stromal) cells (MSCs). Later it was found that they are located not only in bone marrow but also in many tissues of the body, including fat and liver, plus peripheral and umbilical cord blood, which makes them more obtainable for sampling and harvesting.
MSCs Mechanisms of Action
Although the MSCs ability to differentiate into different types of cells is hindered in vivo, scientists have highlighted their overall therapeutic potential. Mesenchymal stem cells have various valuable features, the most beneficial of which is the ability to migrate to the site of injury and produce a cocktail of active biological molecules which differs significantly depending on the environment of the damaged tissue. It can be a specific aid for many health conditions. Via these active substances, MSCs positively affect almost all types of tissues and organs. What is most striking – they can influence the cells of the immune system and reduce inflammation. The latter is one of the main underlying factors in the development of almost any disorder.
Clinical Applications of MSCs
Stem cells have been widely explored for several therapies, and scientific groups achieved legitimate success in employing them for specific indications. MSCs penetrate and assimilate in multiple organs, help repair cardiovascular, lung and spinal cord injuries, and improve the state in autoimmune diseases, liver, bone and cartilage diseases.
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Multiple sclerosis is a chronic disease where inflammation is caused by the failure of the immune system, which damages cells of the brain or spinal cord. MSCs have been shown to reduce the inflammatory response, stimulate neuronal stem cell differentiation, and promote the regeneration of damaged areas in the central nervous system.
Both animal models and clinical trials showed that using MSCs promoted improvement in cardiac repair through stimulation of regeneration of cardiac tissues, as well as through immunomodulation. These cells migrated into sites of myocardial damage and produced a variety of growth factors, which stimulated regeneration of blood vessels, increased cell division and the patient’s survival rate.
Diabetes and Diabetic Ulcer
Diabetes is a widespread disease that is characterised by an increased level of blood sugar (glucose). It occurs when the pancreas fails to produce enough insulin to utilise glucose. High blood sugar is responsible for the negative consequences of this disorder – deterioration in the heart, blood vessels, nerves, eyes and kidneys.
The latest studies have shown that MSCs can control hyperglycaemia by stimulating the regeneration of pancreas cells and protecting them from further destruction. In patients with diabetic ulcers, MSCs improve the microvascular network, i.e. they promote restoration of blood circulation in ulcerative lesions and, as a result, heal the ulcer.
MSCs are known to help in managing autism. The following improvements were demonstrated in the corresponding study:
- better social relationships,
- normalisation of speech,
- increased cognitive function.
The patients also demonstrated more stable behaviour and emotional control. The purported explanation for these effects is that stem cells improve neuron function and metabolism in the brain by increasing oxygenation and blood circulation.
The regenerative benefits of mesenchymal stem cells have been demonstrated for the treatment of both acute and chronic liver failure. The MSC-based approach is less invasive than conventional organ transplantation; it does not have such limitations as lack of donors, liver-graft rejection and post-surgical complications. MSCs in the liver act via the release of trophic factors inhibiting the function of NK cells (liver-specific immune cells) and stellate cells (fat-storing cells) which are responsible for hepatic fibrosis and deterioration of liver function.
Crohn’s disease is another chronic inflammatory disorder. Its exact cause and effective treatment are still not identified. Patients with Crohn’s disease suffer from relapses of severe pain associated with inflammation in their gastrointestinal tract. This condition has a high risk of infections due to a weakened immune system and multiple surgical interventions.
MSCs-based therapies have recently been proposed for treatment of this unrelenting disorder. Several studies were conducted, which supported the suggestion that MSCs could improve Crohn’s disease due to their anti-inflammatory properties. Many patients in these studies demonstrated positive clinical responses and are now in remission.
Fibromyalgia is a chronic condition where muscle pain is experienced throughout the body, which is accompanied by fatigue, sleep loss, depression and decreased cognitive function. Based on more recent assumptions on the autoimmune nature of the disease, plus the positive results of stem cell-based approach in patients with neurological and musculoskeletal disorders, MSC treatment has also been suggested for fibromyalgia. The pain and other neurological symptoms which are common in patients with this condition are caused by inflammation, and this is one of the fields where MSCs prove most useful.
Both preclinical and clinical studies confirmed that treatment with MSCs results in a reduction of symptoms and even slows down the progression of this disease. It allows patients to avoid the adverse effects of medications currently used for the management of this incurable disorder.
Injuries and Musculoskeletal Pain
The administration of MSCs helps muscle recovery after injury, enhances muscle force, promotes peripheral nerve regeneration, stimulates blood circulation and growth of blood vessels at the injured site. By modulating inflammation stem cells, it improves the healing process, prevents scar tissue formation and restores the natural mechanical function of the organ.
Stem cells are now frequently used for the treatment of pain when conventional medicine proves to be ineffective (for example, severe osteoarthritis, neuropathic pain etc.) The pain-relieving function of MSCs is also based on their ability to reduce inflammation and protect tissues from degeneration.
A pilot study conducted in China showed promising results among critically ill COVID-19 patients. The immune-modulating effect of MSCs prevented a cytokine storm and improved the outcome of patients with pneumonia caused by SARS-CoV-2. Numerous ongoing studies around the world should clarify the exact mechanism of this action, but now it is confirmed that MSCs transplantation can be beneficial for treatment COVID-19 complications.
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What Is Stem Cell Therapy?
The standard treatment procedure in most clinics includes several steps. First, the patient undergoes physical examination by a doctor, who collects their medical history, and then they have a consultation with specialists. The medical staff then determine the best treatment strategy for the patient. It includes decisions regarding:
- the source of stem cells (whether the patient’s cells or a donor cell product is to be used),
- the route of stem cell administration,
- the therapeutic regimen.
In some cases, concomitant treatment may be advised for the most beneficial results.
When the patient’s (own) cells are used, they are harvested from bone marrow, fat tissue, venous blood, or the mucous membrane of the gingiva. Then they are processed, which may take several days. As a result, the prepared cell product, with the required characteristics, is then introduced into the patient’s body locally and/or via systemic administration.
According to current clinical practice, there are no severe side effects of such treatment. The first effects of stem cell treatment may be observed within a week of administration. However, full improvement is reached in several weeks, as the regeneration mechanisms initiated by transplanted cells need time to become established.
Stems cells are a potent tool for the treatment of diseases caused by inflammation, immune system failure and/or tissue degeneration. These types of cells provide excellent results in areas where conventional medicine is still losing the race. Scientists around the world are carrying out clinical trials and research for a more profound understanding of the mechanisms underlying the therapeutic effect of MSCs, to improve the successful experience in the therapy of many diseases and conditions.
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