Adipose Tissue-Derived Stem Cells in Regenerative Medicine

Adipose Tissue-Derived Stem Cells in Regenerative Medicine

Regenerative medicine is a field of research concerned with the process of replacing diseased, dying, or dead cells with the intent of restoring structure and function. In its most basic form, regenerative medicine seeks to regrow cells that were lost or damaged due to injury or condition. Examples of regenerative medicine applications include restoring heart cells after a heart attack, repairing brain cells in Alzheimer’s disease or after stroke, or regenerating T-cells in HIV/AIDS. The potential applications of regenerative medicine are virtually limitless.

Adipose-derived stem cells hold great promise in the field of regenerative medicine. The stem cells are multipotent, which means they can become any number of cell types. For example, adipose-derived stem cells can become osteocytes (bone cells), neural cells (nerve cells), vascular endothelial cells (cells that make up blood vessels), cardiomyocytes (heart muscle cells), pancreatic β-cells (cells that produce insulin), and hepatocytes (liver cells).

Adipose- or fat-derived stem cells have one obvious advantage over bone marrow cells: they are much easier to obtain. Bone marrow stem cells require an uncomfortable/painful procedure to extract them from the center of the bone. Fat-derived stem cells, on the other hand, can be taken from fat pockets in any number of places just under the skin. This essentially combines a sort of liposuction with stem cell transplantation.

Adipose-derived stem cells are the subject of nearly 200 clinical trials worldwide. Even now, fat-derived stem cells are proving useful in several clinical conditions. Adipose-derived stem cells were shown to help people after they suffered from a heart attack, by reducing the size of the damaged heart and helping to restore heart function.

Another advantage of adipose-derived stem cells is that they present possess a tri-germ lineage differentiation potential, meaning they can differentiate into all three germ layers. In other words, they have the remarkable potential to become virtually any cell in the body. This means they can be applied to more than one disease state. In neurodegenerative diseases, such as post-stroke, adipose-derived stem cells could be used to create nerve cells (neurons) and the other main type of brain cell, called glia. Both cell types are destroyed during a stroke, and both are important for proper brain function.

As more results are published from dozens of clinical trials, we will get a clearer picture of the therapeutic potential of adipose-derived stem cells. Indeed, the future of regenerative medicine is very bright.

Hyperbaric Oxygen Moves Stem Cells from Bone Marrow to Bloodstream

Hyperbaric Oxygen Moves Stem Cells from Bone Marrow to Bloodstream

Stem cells are generating so much excitement in research and clinical circles because they have the capacity to become many other types of cells. They also release a number of important molecules such as hormones, cytokines, and genetic material that can potentially be helpful for patients. Researchers have found that not only does hyperbaric oxygen therapy (HBOT) help in the circulation of stem cells but it also will help to mobilize stem cells from the bone marrow to the bloodstream further preparing the patient for stem cell therapy.

Bone marrow is a rich source of stem cells, but getting them usually requires an invasive procedure, i.e., placing a large bore needle into the middle of bone(s). Researchers have discovered, however, that hyperbaric oxygen treatment causes stem cells from the bone marrow to move into the bloodstream by specifically stimulating the body’s nitric oxide synthesis. Thus, instead of using a needle to extract stem cells from the bone marrow, patients can potentially increase their own bone marrow stem cells by undergoing hyperbaric oxygen treatment.

Stephen Thom, MD, Ph.D. and co-researchers at the University of Pennsylvania showed that a single hyperbaric oxygen treatment could double the number of bone marrow stem cells in the blood. This means that the hyperbaric oxygen was “mobilizing” the stem cells to move from the bone marrow into the bloodstream to allow them to move into areas of the body that benefit from them. Moreover, when study subjects underwent 20 treatments of hyperbaric oxygen therapy over a few weeks, the number of bone marrow stem cells in the blood increased significantly by eightfold. This astonishing finding has been confirmed in subsequent experiments.

The most important conclusion from this research is that hyperbaric oxygen therapy treatments can unlock the potential of a person’s own bone marrow stem cells without an invasive procedure. While many scientists assumed that the benefits of hyperbaric oxygen therapy were due to the high concentrations of oxygen infusing the blood, tissues, and cells, they now have research to support that these benefits may also be due to stem cell mobilization.

Extracellular vesicles derived from bone marrow mesenchymal stem cells protects against experimental colitis

Extracellular vesicles derived from bone marrow mesenchymal stem cells protects against experimental colitis

Colitis is inflammation of the colon, also known as the large intestine. Several things can cause colitis such as infection, medication, ischemia, or chronic inflammatory bowel disease.  Inflammatory bowel diseases that affect the colon, such as ulcerative colitis or Crohn’s disease, are particularly challenging for patients. It is a chronic disease that causes cramping pain, bloody diarrhea, weight loss, fatigue, and many other chronic, challenging symptoms.

Since ulcerative colitis does not occur naturally in animals, researchers sometimes use an experimental form of colitis to mimic the disease seen in humans. This experimental colitis serves as a model to investigate treatments for inflammatory bowel disease. Essentially, researchers create a situation in which mice develop a condition that looks very much like ulcerative colitis. They develop inflammation in the large intestine, along with signs of oxidative stress and cell death. Conversely, treatments for ulcerative colitis reduce or prevent inflammation, oxidative stress, and cell death in the colon of these experimental mice.

Researchers used this model of experimental colitis to study the effect of bone marrow stem cells as a treatment for colitis. More specifically, they tested the effects of a certain part of bone marrow stem cells called extracellular vesicles. Extracellular vesicles are small spheres that containing various beneficial substances. Stem cells release these vesicles into the body. A single stem cell can release hundreds of extracellular vesicles. In fact, it is the extracellular vesicles that are believed to contain many of the useful substances that are released by bone marrow stem cells such as proteins, lipids, and nucleic acids. These substances can precisely target sick and damaged cells in the body and repair them.

Impressively, when researchers used extracellular vesicles derived from bone marrow stem cells to treat animals with experimental colitis, they observed rather extraordinary results. These vesicles protected the intestines from colitis damage. Untreated animals had severely damaged intestines when viewed under a microscope, but animals treated with extracellular vesicles had nearly normal looking intestines. Treatment also substantially reduced levels of cytokines related to oxidative stress, such as IL-1β. Extracellular vesicles derived from bone marrow stem cells also apparently blocked the intestinal cells’ ability to undergo cell suicide (apoptosis).

Taken together, these results strongly suggest that mesenchymal stem cells from bone marrow, specifically the extracellular vesicles contained within them, can dramatically improve experimental colitis. While more research is needed, this study suggests that these stem cell products could one day be a useful treatment for inflammatory bowel diseases, such as ulcerative colitis and inflammatory bowel disease.

Intravenous Stem Cells in the Treatment of Inflammatory Bowel Disease

Intravenous Stem Cells in the Treatment of Inflammatory Bowel Disease

Ulcerative colitis and Crohn’s disease, together known as inflammatory bowel disease, are chronic disorders of the lower digestive tract that cause patients considerable difficulty and discomfort. Patients generally go through periods of normalcy punctuated by relapses. In cases of inflammatory bowel disease, patients may experience severe, and sometimes bloody diarrhea. Patients also experience crampy abdominal pain, the urgent need to defecate, pain with defecation and even fecal incontinence. Consequently, people with inflammatory disease often endure substantial amounts of suffering.

Inflammatory bowel disease is usually treated with 5-aminosalicylate or sulfasalazine. These drugs are intended to reduce inflammation in the bowels. Relapses do still occur for those patients taking these medicines. During these relapses, patients often need to take steroids for short or intermediate periods of time but over time, side effects can occur. Immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate can be used to reduce inflammation, however, these drugs can also cause side effects. Newer biologic response modifiers have helped people with severe inflammatory bowel disease but they may weaken the body’s immune system, making it more difficult to fight off infection. For these reasons, safer and more effective treatments for inflammatory bowel disease are needed.

Fortunately, researchers have conducted a number of clinical studies examining the role of stem cells in the treatment of inflammatory bowel disease. The most promising results have come from allogeneic mesenchymal stem cell therapy using stem cells derived from the umbilical cord. Research has found that allogeneic mesenchymal stem cells injected into a vein were able to induce a clinical response 3 out of 9 patients tested. One patient had complete clinical remission. In all cases, the stem cells increased the quality of life for patients. Five out of seven patients with inflammatory bowel disease had clinical remission after stem cell treatment. Likewise, further research showed that the stem cells could induce a clinical response and 12 of 15 patients and full clinical remission in eight of them. Here too, patients reported improved quality of life with stem cell treatment.

These results are incredibly promising and offer hope to patients struggling with ulcerative colitis and Crohn’s disease. While more research is needed, patients with inflammatory bowel disease should follow this field closely for new developments.

Mesenchymal Stem Cells Show Promise for Treating Silicosis

Mesenchymal Stem Cells Show Promise for Treating Silicosis

Silicosis, which is also known as miner’s phthisis, potter’s rot grinder’s asthma, potter’s rot, is an occupational disease of the lungs that is caused by the inhalation of a specific type of dust called crystalline silica dust. The disease causes inflammation and scarring in the lungs that leads to the formation of lesions. The disease has been increasing in incidence in developing countries in recent years and unfortunately cannot be fully cured.

A recent study, published in Stem Cell Research & Therapy, explored, for the first time, the potential to intervene in processes associated with silicosis. Stem cell therapy has been used to address inflammation and the resulting tissue damage. Mesenchymal stem cells have been applied to other occupational conditions as well. The researchers hypothesized that adipose-derived mesenchymal stem cells would improve pulmonary fibrosis by reducing inflammation.

Through their study, they found that using these adipose-derived mesenchymal stem cells in silicosis did indeed lead to a remissive effect with regard to pulmonary fibrosis. Further, they found that this occurred by reducing inflammation by modifying protein certain cellular pathways that decreased the expression of problematic proteins.

While this data is preliminary, they show the potential promise of stem cells in the therapeutic intervention of silicosis. Future studies will help researchers and clinicians better understand how stem cells can be used to combat the pulmonary fibrosis associated with silicosis, as well as how they can be used to combat other occupational diseases.

 

 

 

Stem Cell Mobilization Is Enhanced with Higher Pressure Oxygen Therapy

Stem Cell Mobilization Is Enhanced with Higher Pressure Oxygen Therapy

While most approaches to stem therapy involve infusing purified stem cells into the body, Thom and fellow researchers have shown that hyperbaric oxygen therapy (HBOT) is capable of stimulating the body to produce its own stem cells. Thom, Heyboer, and co-authors have extended this work by showing that by slightly increasing the pressures used during hyperbaric oxygen therapy, one can significantly increase the number of stem cells produced.

In his original work, Thom and colleagues showed that a single, two-hour session of 2.0 atmospheres (atm) pressure (twice the air pressure we normally feel at sea level) was capable of doubling the number of stem cells in the bloodstream. Twenty treatments increased stem cell levels by 800%. To study this phenomenon more closely, Thom’s research group recruited 20 patients to undergo hyperbaric oxygen treatment, some at the original 2.0 atm pressure, and some at 2.5 atm. The primary goal of this research was to find out whether a higher pressure was capable of eliciting a greater number of cells.

As before, treatment with 2.0 atm of hyperbaric oxygen substantially increased the number of stem cells found in the blood. However, treatment with 2.5 atm doubled or even tripled the number of stem cells produced compared to the 2.0 atm treatment session. In other words, a slightly higher pressure causes the body to produce substantially more of its own stem cells.

Researchers focused on two types of stem cells, in particular, CD34+ and CD45-dim—markers that appear on stem cells and/or progenitor cells. They are primarily found on cells in the bone marrow. Stem cells with CD45-dim generally go on to become bone, blood, or blood vessel cells, while CD34+ cells can differentiate into almost any cell. Hyperbaric oxygen therapy is thought to stimulate the bone marrow to produce and release these stem cells into the bloodstream, which is the reason these treatments raise stem cell levels in the blood.

The results published by Thom and coworkers suggest that patients who wish to enhance the number of stem cells should consider undergoing hyperbaric oxygen therapy. Furthermore, the greatest number of stem cells was observed after 20 treatment sessions, suggesting that a greater effect occurs with more treatments.

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