The evidence for the promise of mesenchymal stem cells in regenerative medicine has been growing for several years. With new sources regularly emerging, stem cells can come from a large variety of sources. Postnatal mesenchymal stem cells appear to have the most promise in regeneration. A new review has addressed how mesenchymal stem cells can be used with innovative scaffolding engineering approaches to improve techniques in regenerative medicine.
Mesenchymal stem cells are, on their own, good candidates for regeneration because of a number of characteristic features. For instance, they can differentiate into many different types of cells. Osteoblasts and chondroblasts are two cell types that mesenchymal stem cells differentiate into and that can be supported in bone regeneration by 3D-printed biomaterials like scaffolds.
Mesenchymal stem cells also can have beneficial impacts on the immune system. Unlike with other stem cell types, the severe immune reactions that may occur with the transplantation of foreign materials into the body can often be avoided with the use of mesenchymal stem cells, making them a safe option in regenerative medicine.
The current review addresses the ways in which bone regeneration can be optimized through the use of mesenchymal stem cells and scaffold engineering and how new concepts in bioengineering may be able to improve regenerative medicine in combination with mesenchymal stem cell approaches. Future research will need to focus on how we can customize regenerative approaches using what we know about mesenchymal stem cells and the most cutting-edge innovations in bioengineering.
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.
Mesenchymal stem cells have been showing promise in the treatment of a variety of diseases and injuries. These cells are derived from different tissue types, and it appears that where the stem cells come from is indicative of how they function and how appropriate they are for use in different applications. Bone marrow-derived mesenchymal stem cells have been deeply studied and are often considered a go-to for stem cell research and clinical use.
However, there are several limitations that bone marrow-derived mesenchymal stem cells pose, particularly from a practicality standpoint, and thus, researchers have begun to try to understand how other types of stem cells may achieve similar or better results than those from the bone marrow. A recent review, published in Act Histochemical, compiled comprehensive data on the biological properties associated with a specific type of mesenchymal stem cell called Wharton’s Jelly-derived mesenchymal stem cells.
These stem cells, which come from the umbilical cord, are able to differentiate into mature cells that make up several different types of tissues and can even turn into non-mesenchymal cells, such as neurons, or brain cells. They are useful in that they spontaneously move to sites of injury or inflammation and may, therefore, be able to help restore tissue and normal functioning. They are also unlikely to instigate adverse immune system reactions.
While it is advantageous that bone marrow-derived mesenchymal stem cells have been studied extensively and therefore are associated with broad knowledge of therapeutic applicability, the cells are difficult to isolate and use. In contract, cells from the umbilical cord matrix, or Wharton’s jelly, are easy to isolate and also appear to be good candidates for therapeutic intervention. Future research should therefore look more closely at how Wharton’s jelly-derived mesenchymal stem cells can be used to treat disease and injury. As noted by the authors of this review, there are specifically dysfunctions of the central and peripheral nervous system that these stem cells may be able to address.
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.
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.
As patients start to investigate the many different types of stem cells, it can become overwhelming. Often stem cells are organized into groups by tissue source, i.e., by the type of tissue stem were derived. While it can be important to know whether stem cells come from adipose tissue (fat cells) or the umbilical cord, for example, it is equally important to understand the types of stem cells by their capacity to differentiate. In other words, what are the types of stem cells organized by their ability to become different or more mature cells?
One of the most intriguing features of stem cells is their ability to become virtually any other type of cell. We all start out as a sperm and an egg but end up as an exquisitely organized collection of heart cells and brain cells and kidney cells, etc. At each step of the way—from early cells to the adult human body—stem cells become more differentiated and less capable of becoming any other cell. Thinking about them this way, stem cells are grouped into four categories:
Omnipotent stem cells
Pluripotent stem cells
Multipotent stem cells
Unipotent stem cells
Omnipotent stem cells
Omnipotent stem cells, also called totipotent stem cells, truly have the capacity to become any other cell. Omnipotent stem cells can become embryonic cells or even the cells that support the embryo, like the placenta. A fertilized egg is an example of an omnipotent cell. While omnipotent/totipotent stem cells are potentially incredibly useful, their use is highly restricted and controversial. As such, they are not usually used for therapeutic purposes, or even for research.
Pluripotent stem cells
Pluripotent stem cells are the next best thing to omnipotent stem cells. Pluripotent stem cells can become nearly any tissue in the body. Like omnipotent stem cells, the use of naturally occurring pluripotent stem cells is also controversial because they require the use of embryos. However, researchers have devised a rather ingenious way to take regular cells and turn them into pluripotent stem cells. These stem cells are referred to as induced pluripotent stem cells or iPSCs. Induced pluripotent stem cells are particularly exciting because of their potential as research tools and clinical therapeutics. Most importantly, iPSCs sidestep controversy because they are made from mature cells.
Multipotent stem cells
Multipotent stem cells can become any number of mature cells. For example, a mesenchymal stem cell can become a muscle cell or fat cell, a bone cell or cartilage cell. Another powerful feature of multipotent stem cells is that they can divide and form other multipotent stem cells. Thus, their ability to differentiate and self-renew makes them incredibly versatile for research and clinical purposes.
Another example of multipotent stem cells is the type of cells that give rise to blood cells, namely hematopoietic stem cells. Hematopoietic stem cells can differentiate into myeloid type or lymphoid type, but once they do, they are restricted to become their corresponding type of blood cell. For example, myeloid cells can become red blood cells or certain white blood cells, while lymphoid cells are more or less destined to become lymphocytes.
Unipotent stem cells
Unipotent stem cells are technically stem cells but have very little potential become anything other than the one cell they were destined to become. For example, a cartilage stem cell is destined to become a cartilage cell, while a bone stem cell is destined to become a bone cell. A mesenchymal stem cell could become either one, but by the time it has differentiated into a cartilage or bone stem cell, its fate is essentially predetermined. As you may expect, unipotent stem cells have limited clinical usefulness.
In summary, as you think about different types of stem cells, it can be important to think about where the stem cell came from (e.g. fat tissue), but also consider its potential for self-renewal and differentiation.
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