Autoimmune disorders are conditions in which the sufferer’s body produces substances that attack the healthy cells of the organism, as it doesn’t distinguish between the healthy tissues and antigens. There are more than 80 types of autoimmune conditions known today, among which diabetes type 1, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, myasthenia gravis and multiple sclerosis.
The exact cause of these ailments is unknown, but scientists believe that viruses, bacteria or certain drugs may trigger some internal changes that confuse the organism and cause the immune system to react by destroying the healthy tissues. Besides the damage caused to healthy cells, autoimmune conditions also lead to changes in organ function and may cause the abnormal growth of organs.
These disorders may affect several tissues or organs, but the most common areas that are destroyed by the immune system include the red blood cells, skin, connective tissues, blood vessels, endocrine glands (mostly the pancreas and thyroid), joints and muscles.
Currently, the standard treatment for autoimmune conditions is represented by immune suppressive agents, but these medications only induce temporary improvements, and don’t cure the disorders completely. For this reason, scientists have started to investigate the potential use of stem cells in autoimmune disorders.
In animal studies, stem cell therapy with mesenchymal stem cells has been shown to induce healing activity in various autoimmune disorders, and to prevent the destruction of healthy tissues by the immune system. But what does research say about treating autoimmune disorders in humans? Are stem cells effective in this case as well?
THE USE OF STEM CELLS IN AUTOIMMUNE DISORDERS IN HUMANS
Mesenchymal stromal stem cells have been found to exert immunological functions under inflammatory conditions, a study published by researchers at the Department of Internal Medicine, Erasmus MC, Rotterdam in Arthritis Research and Therapy showing that MSCs play an important role in maintaining immune homeostasis [1].
According to researchers, MSCs do not have immune cell effector functions and are not “true” immune cells, but can play a role in the initiation of immune responses. Unlike immune T- and B-cells, mesenchymal stem cells do not poses receptors for recognizing the antigens, but they do express pattern recognition receptors, which enable the stem cells to recognize microbes.
In conclusion, the mentioned study showed that although MSCs do not fit the exact definition of immune cells, they do influence the body’s immune response and can act as regulators or coordinators of the immune system [1].
In another paper published in the Nature journal, scientists at the Massachusetts General Hospital, Harvard Medical School have showed that hematopoietic stem cells may be used in treating severe autoimmune diseases, like rheumatoid arthritis or multiple sclerosis [2].
The stem cell therapy investigated by the US researchers involved the transplantation of HSC following an immunosuppressive treatment like chemotherapy or radiotherapy. This treatment was found to be effective in curing autoimmune diseases in animal models, and most patients who received allo-HCT achieved remission of the disorder, although there were also exceptions.
Researchers at the Stem Cell Technology Research Center, Tehran have investigated the use of stem cell therapy in multiple sclerosis patients. Their review paper, published in the International Journal of Hematology-Oncology and Stem Cell Research, showed the following: neural stem cells derived from the adult central nervous system may have neuroprotective and immunomodulatory effects, so they may be a solution for treating MS [3].
Mesenchymal stem cells derived from bone marrow also have a potential for migration into the inflamed tissues of the central nervous system and are able to differentiate into neuronal cells. In mice, MSCs helped in improving the neurological function of animals with experimental autoimmune encephalomyelitis (EAE). The application of stem cells in humans with multiple sclerosis was also investigated by scientists at the American University of Beirut Medical Center, Lebanon, who showed that bone marrow mesenchymal stem cells may lead to clinical improvements in patients with advanced multiple sclerosis [4].
Another autoimmune condition in which stem cells may be useful is rheumatoid arthritis, studies showing that human amnion mesenchymal cells isolated from the placenta may be feasible for treating collagen-induced arthritis in rats [5]. These cells have immunosuppressive functions and can ameliorate the severity of arthritis, so they may be a promising therapy for RA sufferers.
Despite these positive results, there are still a lot of challenges to overcome when it comes to treating autoimmune disorders with stem cells, so scientists need to establish precise protocols for all these conditions that could be treated through stem cells therapy.
References:
[1] http://www.arthritis-research.com/content/17/1/88
[2] http://www.nature.com/nature/journal/v435/n7042/full/nature03728.html
[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913133/
[4] http://www.ncbi.nlm.nih.gov/pubmed/20728948
[5] http://www.ncbi.nlm.nih.gov/pubmed/25962385

Cartilage and bone deterioration are a common consequence of aging, but poor diet, sedentary lifestyle, excess weight or injury can also result in damaged tissue. Unlike bone tissue, mature cartilage is avascular and doesn’t heal well after injury. Replacement or augmentation surgery is one way to fix a torn joint, but the costs are high and there are also several risks involved in the procedure, such as transplant rejection and infection [1].
In January 2015, scientists at the Stanford University School of Medicine published a paper regarding their latest findings in tissue engineering. With the use of skeletal stem cells (myoblasts), they have been able to give rise to bone and cartilage in mice. In addition, they mapped out the chemical signals which can create skeletal muscle stem cells, directing their development into specialized types of cells [2].
To better understand the medical significance of these findings, we are going to take a closer look at stem cells and their role in bone and cartilage regeneration.
HOW SKELETAL STEM CELLS ARE OBTAINED
Stem cells (or blank cells) are undifferentiated cells that can divide or differentiate into specialized cells, replacing dying cells or damaged tissues. There are two broad types of stem cells: embryonic stem cells (ESCs) and adult stem cells (somatic stem cells).
ESCs are harvested from embryos 4-5 days post-fertilization, at each time they consist of 50-150 cells. Embryonic stem cells are pluripotent and can repair damaged tissue or stimulate the regeneration of diseased cells. However, due to ethical controversy, the study of ESCs is a slow process.
In humans, bone marrow, peripheral blood and adipose tissue are rich sources of adult stem cells, but these can be also harvested from some brain areas, skin, liver and even teeth. Until recent years, it was thought that adult stem cells differentiate only as the type of tissue they originate from. Emerging studies suggest that just like ESCs, these cells can specialize in unrelated cell types, as well.
The study conducted at the Stanford University School of Medicine supports these claims. The research focused on groups of cells with a fast division rate, located at the ends of mouse bones. Human skeletal muscle-derived cells were transplanted into host mice.
Prior to the procedure, the targeted host tissues were modulated by irradiation and cryoinjury, to allow the observation of the transplanted cells in mice. After four weeks of observation it was discovered that these isolated collections of cells were able to reconstruct all parts of the mouse bone.
Through further investigation, scientists were able to map the developmental tree of skeletal stem cells, which provided great insight on how to give rise to more specific types of cells. Irving Weissman, MD professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine, hopes that once these findings are translated into humans, the odds of rescuing cartilage and bone from wear and aging will increase significantly [3].
DIFFERENTIATION OF SKELETAL STEM CELLS AND THERAPEUTIC APPLICATIONS
Skeletal muscle is a dynamic tissue, capable of a regenerative response within a couple of weeks. This ability is primarily due to its satellite cells populations, a type of cells that are located peripheral to the myofiber.
When injury or disruption occurs, these satellite cells become activated and either fuse together to replace the damaged myofiber or multiply at an increased rate, supporting additional rounds of regeneration. In addition, skeletal stem cells can also give rise to blood derivatives, vascular components, osteoblasts (bone formation cells), adipocytes (fat cells) and cartilage [4].
The use of skeletal stem cells for therapeutic purposes brings hope to patients who suffer from muscular conditions, including muscular dystrophy. Joint pain, dislocations and arthritis are also on the list of potential stem cell therapy. Rheumatoid arthritis, Osteoarthritis and even Multiple Sclerosis patients could also benefit from these findings in the not-too-distant future.
The main challenge of using myoblasts for cell therapy remains, for now, harvesting and culturing them up to the numbers required.
References
[1] David King – Development and remodeling of skeletal tissue, School of Medicine, Southern Illinois University, 2009 http://www.siumed.edu/~dking2/ssb/skeleton.htm#development
[2] Christopher Vaughan – Researchers isolate stem cell that gives rise to bones, cartilage in mice, Stanford Institute for Stem Cell Biology and Regenerative Medicine, 2015 https://med.stanford.edu/news/all-news/2015/01/researchers-isolate-stem-cell-that-gives-rise-to-bones-cartilage.html
[3] http://www.stemcellclinic.net/tag/stanford
[4] http://genesdev.cshlp.org/content/20/13/1692.long

The loss of bone mass and the weakening of the bones are natural consequences of aging, but this process starts around the age of 30, so it’s not only the elderly that are at risk for falls and fractures due to bone resorption.
Some of the factors that cause the decrease in bone mass density can be controlled, but others are out of one’s control. Smoking for example can be avoided, and one can practice strength exercises to keep their bones strong, but an inadequate intake of calcium, the use of asthma medications, as well as the changes in hormone levels that occur in older adults can speed up the weakening of bones.
Also, this process is accelerated by an inadequate intake of vitamin D, the lack of exposure to gravity and hypoparathyroidism, all these factors favoring the resorption of bone. When the tissue is broken down faster than it can be renewed, the density of bones starts to decrease and they become more porous, fragile and prone to fractures.
Although there are a series of conventional treatments that can help in improving bone density in osteoporotic patients, people who suffer multiple fractures, major bone trauma or individuals injured during natural disasters may require a different approach. In such cases, the use of stem cells could speed up bone repair and eliminate the risk of tumor formation.
STEM CELLS FROM BONES AND SKIN, USED FOR BONE RECONSTRUCTION
Scientists from the Gladstone Institutes have discovered a way to stimulate bone reconstruction using proteins produced by stem cells. Instead of grinding up bones from cadavers in order to extract the proteins and growth factors needed for stimulating the growth of new tissue, the researchers have extracted bone-forming proteins from stem cells.
After they treated the proteins in the lab, they injected the substances into muscle tissue of mice, in order to facilitate bone growth. The injected proteins were effective in creating new bone tissue, so there is hope that this method may be a good solution for humans as well. Unlike current treatments, the use of stem cells is safer as it doesn’t involve the transplant of cells or tissues from cadavers or other donors, so the risk for these cells to be rejected is much lower and the risk for tumor formation is very low also.
The study published in Scientific Reports concluded that proteins extracted from stem cells could be a consistent and reproducible source material for tissue regeneration [1]. This isn’t the first study to support the use of stem cells for orthopedic purposes. In 2001, another paper published by Dr. Ranieri Cancedda in the New England Journal of Medicine described the use of autologous bone marrow cells in the repairing of large bone defects.
The research showed that the osteoprogenitor cells derived from stem cells were effective in supporting the integration of macroporous hydroxyapatite scaffolds in damaged bones. Three patients were treated using this method and CT scans taken 6 months afterwards showed good callus formation and integration of the interfaces in all patients [2].
Even more interesting were the results obtained by a team of scientists from the National Institutes of Health, Bethesda, USA, who managed to grow new bone from stem cells harvested from skin cells. The paper was published in the Cell Reports journal, the harvested skin cells being reprogramed into equivalents of embryonic stem cells [3]. The obtained iPSCs were treated in lab conditions to differentiate into precursors of bone cells, then transplanted the obtained cells into monkeys, on a ceramic scaffold.
The implanted cells grew new bone on top of the scaffolds, researchers finding no sign of tumor. According to the researchers, this technique has two great advantages: the stem cells harvested from patient’s own cells are less likely to be attacked by one’s immune system, and iPSCs can be generated from any individual.
Although the use of stem cells for speeding up the integration of implants in damaged bones is not new, scientists are now looking to develop these methods further, so as to obtain stem cells that can promote bone regeneration and regrowth once transplanted to humans.
References:
[1] http://gladstoneinstitutes.org/pressrelease/2015-05-11/scientists-regenerate-bone-tissue-using-only-proteins-secreted-by-stem-cells
[2] http://www.healio.com/orthopedics/biologics/news/print/orthopedics-today/%7B45aecb5d-a1c0-4e13-8bf7-607f32a812bf%7D/bone-regeneration-is-possible-using-stem-cells
[3] www.cell.com/cell-reports/abstract/S2211-1247%2814%2900306-4

What seemed an impossible medical challenge a few years ago might turn into a do-able task with the help of bone marrow stem cells. Several trials are testing the use of adult stem cells in heart disease, hoping to identify a viable solution for repairing the cardiac tissue damaged by heart attacks, coronary artery disease and other similar ailments.
<h1>Obtaining cardiac muscle cells in the lab</h1>
Despite the huge amount of information available out there and the numerous health programs that aim to prevent heart diseases, these conditions remain the most common cause of death in Europe, with heart attacks dominating the list. According to statistics, around 7 million people worldwide suffer from heart attacks each year, the damage being in lots of cases irreversible.
Given the amazing results obtained with stem cell therapies in conditions like leukemia or lymphoma, it was natural for scientists to intensify their research efforts in this niche, in order to see whether the potent stem cells can also be used for repairing damaged hearts. While some studies have showed promising results, others have found no improvement after transplanting stem cells to patients with heart conditions.
The biggest challenge in these cases seems to be the reprograming of stem cells obtained from other tissues into cardiomyocytes. Cardiomyocites are the cells that form the cardiac muscle, and although for a very long time scientists believed that the heart does not produce any stem cells, it’s been shown that the body does produce new cardiomyocytes each year, but the number decreases with age.
The discovery that the human heart produces new cells each year has created hope and encouraged researchers to try to find out where the new cardiac cells come from and how this process is controlled inside the body. The ultimate goal was to identify those mechanisms that could be replicated in lab conditions, so as to obtain new heart cells viable for transplantation in patients with heart diseases.
Although the existence of heart stem cells has not been confirmed yet, it is possible to obtain cardiomyocytes in the lab, from stem cells obtained either from embryos or from iPS cells (induced pluripotent stem cells). The latter can be obtained by reprogramming skin cells that are taken directly from the patient, reducing the risk of transplant rejection.
One of the biggest problems here comes from the fact that bone marrow cells and other adult stem cells can be reprogramed to repair a specific tissue, but if they are treated in lab conditions until they differentiate to specific cells like those in the cardiac tissue, the risk of tumors and rejection increases.
On the other hand, if the pluripotent stem cells from embryos or the iPS cells are transplanted into the heart, they might differentiate and give birth to a multitude of cells. It is impossible for one to control the type of cells formed by stem cells in the body once transplanted, if those cells were transplanted before specializing.

Stem cell studies on the damaged heart show mixed results

Existing studies show that treating heart conditions with stem cells is more difficult than using stem cells therapies for other tissues and organs. A trial done in Belgium, Switzerland and Serbia on 45 patients aimed to treat heart attack victims with stem cells. The injected cells led to no complications and were guided to become cardiac cells, scientists highlighting the safety and feasibility of the procedure [1].
Other studies showed little to no effect after the transplantation of stem cells. Cardiologist Darrel Francis at Imperial College London published a review study in BMJ, examining 133 reports of 49 randomized clinical trials that aimed to treat heart attack or heart failure patients with stem cells. According to his paper, more than 600 discrepancies were found in these trials, so the results cannot be considered relevant [2].
Francis’ study showed that the 5 trials that had no discrepancies reported no improvement in the left ventricular ejection fraction (LVEF) after stem cell treatment, while the 5 trials with the most numerous discrepancies reported a significant improvement (+7.7%) of LVEF after stem cell therapy.
While scientists are still trying to answer whether stem cells are a solution for damaged heart tissue, some stories report that patients who received this treatment after a heart attack saw a clear and dramatic improvement in their health state and heart function. One of these patients is Jim Dearing of Louisville, who was among the first patients to receive heart stem cells after suffering two heart attacks and heart failure. His heart was functioning normally one year post treatment [3].
What’s certain for now is that results of these studies are mixed, and researchers will need to further investigate the use of stem cells from bone marrow in patients with heart diseases.
References:
[1] https://beyondthedish.wordpress.com/2014/12/03/mayo-clinic-uses-reprogrammed-stem-cells-to-heal-the-heart/
[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002982/
[3] http://www.webmd.com/heart/features/stem-cells-heart-failure-heart-disease