In this blog, I’ll share some of the results we’ve had using stem cell therapies in different ways to show you how you can utilize them in your office or clinic. Let’s start with stem cell treatments for cosmetic regenerative tissue enhancement. The procedure starts with taking fat from one location on the patient’s body and relocating it to the area you’re trying to enhance and combining that fat with a population of adipose (fat-derived) stem cells for best results.
This theory, in part, was first published back in 2006 by Kotaro Yoshimura, M.D., Associate Professor, Department of PlasticSurgery at the University of Tokyo. Dr. Yoshimura demonstrated that stem cells harvested from fat are actually responsible for creating new adipocytes.
Does this mean fat is our friend? When it comes to therapeutic tissue treatments, it sure is!
We used to believe that we had a set number of adipocytes and that these either grew or shrank depending on the amount of fat that our bodies were gaining or holding, but we now know better. Everyone has a population of stem cells that exist within their fat tissue that is responsible for replacing or replenishing mature adipocytes, and they’ll grow with weight gain. By attaching to fat tissue, those stem cells will actually help support expansion or weight gain. Therefore, you can take stem cells from one sample of fat—imagine all those stem cells clinging to your fat stores—and put them into another sample of fat to create a cell-enriched population that can be utilized to help create angiogenesis (the development of new blood vessels) and help the graft survive better.
Take, for instance, breast augmentation using this process. By taking fat from one location, relocating it, and adding stem cells with the fat to the breast tissue, you can reduce reabsorption of the fat tissue. In addition to being able to perform fat transfer for breast augmentation, you can also utilize the stem cells and platelet-rich plasma (PRP) when you need to rejuvenate the skin as well. One example would be a patient who had received an injection of stem cells plus platelet rich plasma without a fat graft: in this case, the cell will be very angiogenic in nature, creating new blood vessels and generating a youthful glow. The cells can also help with collagen production so the patient gets smoother skin and help with scarring or the appearance of unevenness on the skin.
Adipose stem cells can also be utilized for regenerative results in orthopedics. A typical technique is to isolate the platelet rich plasma from the peripheral blood and combine it with stem cells from the fat tissue. Our preference is to utilize the adipose stem cells, again, because of the massive volume of stem cells fat tissue delivers. We can obtain about five hundred times more mesenchymal type stem cells—stem cells that that can differentiate into a variety of cell types—from adipose tissue than we can obtain from bone marrow. For this reason, in most cases we utilize the cells from the adipose tissue rather than the bone marrow.
This protocol comes courtesy of Joseph Purita, M.D., a member of the Global Stem Cells Group Advisory Board and a pioneer in the use of stem cells and PRP therapy for orthopedic surgery. Dr. Purita’s protocol is to inject the adipose cells plus the PRP interarticularly to the affected joint.
This therapy has also been used successfully in animals. For instance, in the case of a horse with a chronic, non-healing tear in the ligament considered so chronic that they were going to put it down, an injection of the platelet rich plasma plus the adipose stem cells directly into the lesion resulted in a complete resolution of the non-healing ligament within six months post-treatment.
Again, courtesy of Dr. Purita, is another example of a patient with avascular necrosis who had been told that she needed a total knee replacement. She was getting her knee drained once per week, had severe swelling and pain, and was not able to perform, pretty much, any activities due to her joint pain. After injection of the adipose cells plus the PRP, the patient was essentially pain free, she was able to play tennis weekly, and there was complete resolution of the avascular necrosis, according to MRIs six months post-treatment.
Another example is a patient who was hit by a bus and thrown into a house, resulting in a non-union bone fracture that never healed properly. In this case, the patient was treated at the Hospital Angeles in collaboration with the Regenerative Medicine Institute. The patient had not been able to bear weight on the leg for more than two years. After an injection of stem cells plus a bone matrix, at the three-month follow-up there was full continuity down the length of the bone, and for the first time in more than two years, the patient was able to bear weight.
Treatments using adipose (fat)-derived stem cells, in combination with PRP and other regenerative medicine therapies, are proving to provide the body with the ability to heal in cases where nothing else worked. Initial findings tell us that PRP assisted stem cells can figure out what cells they need to replicate—whether cartilage cells, bone cells, or collagen cells for ligaments and tendons—to help the body heal from within.
Global Stem Cells Group is proud to present our 2016 Edition of our Regenerative Medicine Symposium, to be held in 6 different Cities around the World.
This prestigious event will have the presence of a select group of renowned international speakers who will offer a combined day of conferences of high scientific rigor aimed at Physicians.
Global Stem Cells Group’s symposium will provide cutting-edge information on developments in all areas of stem cell research, including the biology, medicine, applications, regulations, product development, and the commercialization of stem cells.
Business opportunities, challenges, and potential strategies for overcoming these challenges will also be addressed. Come join us to learn what categories of companies are currently commercially viable, how they’re being funded, and what kind of strategic relationships are available within the industry
Our First Event of the Year will Take Place in Bogota Colombia in March 3 rd for more info and registration click here http://stemcellconference.org/es/simposio-bogota
Global Stem Cells Group offers a stem cell training course that can help you bring some of our cutting edge regenerative therapies to your practice or clinic. We offer an intensive, hands-on two day training class, show you how to collect fat tissue via our precision mini lipo-aspiration technique, and we walk your through the process of collecting bone marrow via the iliac crest.
We provide didactic lectures on stem cell structure, function and treatment, and we go through the techniques to isolate and harvest stem cells from fat tissue and bone marrow, as well as the platelet rich plasma from the peripheral blood. We do all of this on actual patients! Three to four of them during the two-day course period, so that you can get a good understanding on how to perform the different techniques and procedures.
GSCG will provide you with written protocols, forms and consent so that you can easily implement this in your practice after certification. We also offer instructional videos, quality control (QC) assays, viability and cell counts. Our courses are fully accredited— providing 16 categories for one credit—by three different universities, and we offer the opportunity to participate in Institutional Review Board (IRB) clinical studies.
Now, you’re probably wondering about our products, without which you’d have the weekend off.
For the bone marrow product, we’ve partnered with a company called Emcyte. All of the kits for the bone marrow and the platelet rich plasma are FDA 510K approved, thus allowing for the collection of a small sample of blood, which can be safely attained, to produce concentrated growth factors and platelets. The system is gentle and processes bone marrow aspirate precisely for the purest concentration of cells at the point of care.
Also, there’s our —adipose-derived stem cell Kit . fact: fat tissue is one of the most plentiful sources of stem cells in the body—in particular, the mesenchymal type stem cells. Imagine, you can get about five hundred times more mesenchymal stem cells from fat tissue than you can get from the bone marrow. Fat tissue is a perfect source of stem cells when you’re treating degenerative type diseases, or replenishing some of the tissue that has been damaged as a result of injury and or degenerative disease.
Within this population there exists a multipotential progenitor cell that has the ability to go down the adipogenesis pathway, the chondrogenesis and the osteogenic pathway. These cells are very angiogenic and vasculogenic in nature, meaning they are able to form blood vessels and are very useful in ischemia type conditions.
Global Stem Cells Group has a variety of isolation kits, and all of our kits are produced according to good manufacturing processes as I mentioned before. We have a full scale laboratory in Santiago Chile where we produce all of the reagents that are necessary, and our kits include all of the consumables necessary to isolate regenerative stem cells. You can visit the Adimarket.net website to view the variety of different products we offer, all of which can assist with some of the work you are doing in-clinic. Including things like centrifuges and other medical devices and equipment that are necessary to bring stem cell therapies to the patients. We also go over this information during the stem cell training course and teach you exactly what equipment you will need to perform some of the techniques.
Stem cells have captured the interest of biology nerds, armchair practitioners and everyday individuals for years. Where exactly do they come from and how do they work? When can I have my torn rotary cuff/bum knee /arthritis /(fill in the blank) treated with stem cells? At Global Stem Cells Group, we are making stem cell treatments for a variety of medical conditions available in the physician’s office and out-patient treatment clinics worldwide, and we’re aiming to make them readily available in the U.S. soon, so hang tight.
So, what are stem cells, you ask?
A stem cell is a cell characterized by its ability to self-renew, and its ability to differentiate (change) along multiple pathways. This means a stem cell able is to form specialized cells identical to the cells needed for treatments. For instance, stem cells can become muscle cells, heart cells, skin cells, etc. through stimulation and manipulation via changing chemical environments or genetic triggers. Stem cell physicians know all the tricks to manipulating these uncommitted little units of the body’s rawest materials, and the cells obey!
So, where to find stem cells when you need them?
Different types of stem cells come different sources. We like adult adipose-derived stem cells, which are found in abundance in fat—something there seems to be no shortage of! They can be harvested fairly quickly and painlessly from human body fat, which makes them plentiful and readily available. Each liter of fat produces hundreds of millions of potential stem cells. Other stem cells in the body have been examined for their ability to culture usable induced pluripotent stem cells (iPS cells or iPSCs), which are a type of stem cell that can be generated directly from adult cells.
Adult adipose (fat) stem cells appear to be especially prepped for their job, as they are capable of turning into fat, heart, bone or muscle tissue. We know that these fat cells are multipotent, which means they have the ability to self-renew for long periods of time and differentiate into specialized cells with specific functions, thus creating other types of cells.
Today, Global Stem Cells Group has a validated, compliant outpatient method to provide adipose-derived stem cells, as well as bone marrow-derived stem cells, to physicians for use in in-office procedures. We have trained approximately 500 physicians who are currently offering stem cell therapies in their offices and clinics worldwide, and we’ve only scratched the surface.
So, how exactly do stem cells work?
The concept of stem cell medicine involves the ability to harness the body’s own healing potential to reverse some of the effects of age, degenerative disease and injuries. In other words, we “tell” the stem cells what your body used to be able to do, or how it used to appear, and we have them replicate those youthful, vigorous cells that have not weathered the years or injuries so well.
We often use stem cell therapy interchangeably with regenerative medicine, but this is just one small component of stem cell therapy. We believe the field is going to continue to evolve and move forward, and we’ll be able to combine different techniques to create a truly regenerative response to treatments in patients. The term “stem cell therapy” will eventually become outdated, like when your parents say “groovy.” or “make me a carbon copy.” Instead we will combine techniques like gene therapy and cell therapy in cancers, biologics, scaffolding and delivery systems.
We have really focused on this future in regenerative medicine, combining cellular and gene therapies for use in patients. Everyone in the field is pretty excited about its future, and we believe that regenerative medicine is going to transform medicine as we know it. This is the next big wave for patients who are searching for solutions to their medical needs, but finding few solutions. It’s the 21st century’s version of the polio vaccine, organ transplant and the discovery of antibiotics all rolled up into one—and then some!
Stem cell therapies may hold the cure to Alzheimer’s, although so far that cure has been elusive. People who suffer from Alzheimer’s disease experience disorientation regarding time and place, changes in mood, personality and behavior, memory loss, difficulty solving problems or planning, and difficulty writing or performing other routine and familiar tasks. This progressive and irreversible brain disorder may affect judgment, initiative and social life, and can lead to physical symptoms such as vision problems.
Alzheimer’s affects mostly people aged 70 years and above, and is more common in women. It is the main risk factor for dementia among the elderly.
There is no known cure for Alzheimer’s. Conventional treatments, both drug-based and non-drug strategies, may help with cognitive and behavioral symptoms, but have little to no effect on the disease’s development over the long term. Current medications can’t stop Alzheimer’s from progressing, but they can temporary lessen symptoms like confusion and memory loss.
Although there have been attempts to find a remedy for Alzheimer’s, and despite the fact that scientists have managed to effectively treat lab animals with drug-based treatments, no animal model has managed to truly mimic its symptoms as they manifest in humans. Remedies that worked in lab animals have failed to work in humans; for this reason, scientists decided to try a different approach by exploring the possibilities of stem cells therapies in Alzheimer’s treatments.
Can Stem cells develop new Alzheimer’s treatments?
Alzheimer’s disease affects neurons in all parts of the brain, and the complexity of this condition makes it difficult to create a model that perfectly mimics its manifestations. At least in theory, stem cells could be used for treating this condition by transplanting neural stem cells into the patient’s brain in an attempt to generate healthy new neurons to replace dead and damaged neurons. It remains unclear whether the brain would be able to integrate the transplanted cells, and if the neural stem cells are able to travel to the damaged areas.
Another great challenge is producing the different types of neurons needed to replace the damaged cells, and to find a way to stimulate the renewal of the lost connections between neural cells. Even if the transplanted cells survive and find their way to the damaged areas, they might become damaged by proteins that build up in the brain—the same proteins that cause the disease in the first place, which means any effects of a stem cell transplant could be only temporary.
A different approach would be to use stem cells for delivering neurotrophins to the brain. Neurotrophin proteins support the growth and survival of neurons, but in patients with Alzheimer’s, they’re produced in amounts too low to contribute such support. Neural stem cells can produce such cells, and in mice tests this method did prove helpful; scientists observed some improvements in memory in mice treated with stem cells.
Mesenchymal stem cells could also be used for treating Alzheimer’s—not to replace damaged neurons, but to heal them. Mesenchymal stem cells may exert anti-inflammatory effects and may help ameliorate the symptoms of Alzheimer’s, but there’s no study at the moment to prove their safety or effectiveness in this condition .
Although clinical trials and studies on Alzheimer’s disease treatment to date have a high failure rate, the use of stem cells may be helpful for studying the behavior of brain cells damaged by the condition, as well as for testing various therapeutic approaches and predicting which treatment may help Alzheimer’s patients.
Researchers from the Harvard Stem Cells Institute took skin cells from Alzheimer’s patients and reprogramed them to create induced pluripotent stem cells (iPSC); obtained cells were grown in special lab conditions and were found to release the same proteins that form plaque in Alzheimer’s patients . This may give scientists the opportunity to study the behavior of Alzheimer’s-affected cells and to search for and test new remedies.
Asian scientists managed to turn human fibroblasts into neuronal cells using a chemical cocktail of small molecules . These findings may provide an alternative strategy for modeling the neurodegenerative disorder, which may help scientists understand the mechanisms behind this condition. It may also play an important role in identifying new stem cell based treatments.
The term muscular dystrophy (MD) refers to a group of disorders in which a genetic abnormality causes muscles responsible for controlling movement to become weak, and muscle mass to be lost. These inherited disorders usually affect voluntary (skeletal) muscles, although weakness can also extend to the muscles that control respiration and swallowing.
Given that the genetic mutations triggering MD interfere with the normal production of certain critical proteins, the body is not able to reverse muscle weakening or loss of mass, so even when the disease progresses slowly, it eventually affects one’s ability to walk in a more or less conducive manner.
Who is affected by muscular dystrophy?
In most cases MD appears in infancy, but it’s not uncommon for symptoms to start manifesting in teens or adults.
Although the manifestations are similar, their severity varies depending on the age at which the disease occurs. In some, the symptoms are mild and sufferers are able to continue living almost normally, while in others the ailment is extremely disabling and can lead to muscle wasting, loss of the ability to walk, and even death.
There are different kinds of muscular dystrophy, the most common and severe form being Duchenne muscular dystrophy (DMD) Caused by a genetic flaw or defect, Duchenne MD is more common in males than females [1} and affects about 1 in every 3,500 boys worldwide.
The onset of Duchenne muscular dystrophy occurs between the ages of 2 and 6, and evolves slowly. Muscles becoming weaker year after year, and the spine and limbs becoming progressively deformed. In most cases, children affected by this form of the disease become wheelchair dependent by the age of 12.
People suffering from Duchenne MD often die in their 20s, and those who survive usually experience some degree of cognitive impairment. The shortening of tendons and muscles limits the mobility of sufferers even more, and breathing and heart problems can occur.
Treatments for Duchenne muscular dystrophy
There is currently no known cure for DMD, but there are treatments that help to reduce some of the symptoms and strengthen the patient’s muscles to some degree.
Physiotherapy is commonly used for slowing down the loss of muscle mass and for maintaining flexibility or reducing muscle stiffness. Steroids are also used to slow down muscle wasting, but the severe side effects of steroids often cause more harm than good, such as bone weakening or cardiovascular problems.
In a healthy organism, damaged muscles repair themselves thanks to a series of cells that include muscle stem cells, called satellite cells. In Duchene muscular dystrophy, the muscles lack dystrophin, the protein needed for maintaining the integrity of muscle fibers. Without this protein, the burden placed on the body’s naturally occurring muscle stem cells is too intense, rendering the cells unable to repair damaged muscle tissue or to generate new muscle mass to replace wasted mass .
For this reason, scar tissue and fat cells take the place of damaged muscle tissue, contributing to muscle weakening and, over time, cause muscles to lose their functional ability. Would it be possible for the damaged muscle fibers to regain their regenerative ability with help from transplanted stem cells?
Research suggests stem cells could be a potential solution for muscle wasting
Different strategies involving stem cells for muscular dystrophy may be on the horizon, research suggests. Scientists have been using stem cells isolated from muscle tissue, bone marrow and blood vessels in lab animals to regenerate muscle fibers that are deficient in dystrophin and results are encouraging.
In 2006, researchers managed to restore mobility in two afflicted dogs using stem cells isolated from muscle blood vessels , and in 2007 scientists managed to treat Duchenne MD in research mice using a combination of genetic correction and stem cells . The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles.
Researchers at the Harvard Stem Cell Institute obtained similar results, demonstrating that transplanted muscle stem cells can improve function in mice with MD, while replenishing the stem cell population in muscle fibers .
Although it’s still too early to say whether stem cells can cure DMD in humans, it’s clear that there are some promising stem-cell-based approaches for Duchenne MD. One solution is to replace the defective stem cells with healthy stem cells, as these may be able to generate working muscle fibers to replace damaged muscle fibers .
A second solution would be to reduce the inflammation that speeds up the loss and weakening of muscles using certain types of stem cells . Combined treatments, such as mixing stem cell therapies with gene therapies are also being tested and may prove successful in the near future.
Healing damaged lungs with stem cells.
A New study published by scientists from the Weizmann Institute of Science suggests that stem cells may be used for repairing damaged lung tissue. This discovery gives new hope for treating conditions like bronchitis, asthma, cystic fibrosis or emphysema, which affect more than 35 million Americans and are the second leading cause of death worldwide.
Bone Marrow stem cells able to generate new lung tissue
The treatment method proposed by scientists at the Weizmann Institute is based on the similarities between stem cells that reside in the lungs and those in bone marrow. Bone marrow stem cells, when transplanted to a patient, manage to find their way through the blood and to navigate to the designated area where they differentiate.
Acknowledging the similarities between lung and bone marrow stem cells, Professor Yair Reisner of the Immunology Department of the Weizmann Institute tested the ability of lung stem cells to travel to a specific region after transplantation in mice . Before introducing the bone marrow stem cells into mouse models with lung damage, the group of scientists cleared the lungs’ stem cell compartments to clear a path for the transplanted cells.
The injected stem cells managed to reach the empty lung compartments and settle in the lungs, where they differentiated into normal lung tissue,six weeks after transplantation. Results showed that new lung cells continued to be created from the transplanted stem cells 16 weeks after the implantation, ultimately healing the damaged lungs and improving their breathing ability.
The Weizman scientists intend to continue their research by exploring this option further, and possibly create a bank of lung stem cells that can provide cells ready to be transplanted to patients with severe respiratory diseases.
Lung-specific induced pluripotent stem cells (iPSCs)— potential alternative to bone marrow stem cells
This was not the first attempt to heal damaged lungs with stem cell transplants. In a previous study, scientists from the Boston University Medical Center managed to generate 100 new lines of lung-disease specific iPSC from patients with emphysema, cystic fibrosis and other similar conditions. Results suggest that the new stem cell lines could be used for transplantation in patients suffering from lung diseases, thanks to their ability to differentiate to endoderm cells that give rise to lung tissue.
Darrell Kotton, the study’s lead author, highlighted the fact that iPSCs are easier to cultivate in lab conditions than bone marrow stem cells, and are genetically identical to the patient’s cells, so the risk of rejection in such transplants is eliminated. The lung-specific iPSCs obtained by manipulating adult stem cells into a primitive stem cell state could solve some of the hurdles impacting other kinds of stem cell research.
In this study, scientists used skin stem cells manipulated into primitive pluripotent stem cells, with results showing that the iPSCs have the ability to multiply and differentiate into endoderm tissue–the natural precursor of lung cells .
- Chava Rosen, Elias Shezen, Anna Aronovich, Yael Zlotnikov Klionsky et al. – Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice, Nature Medicine, 2015, http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3889.html
- Aba Somers, Jyh-Chang Jean, Cesar A. Sommer, Amel Omari et al. – Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette, Stem Cells, 2010, 28 (10):1728, http://onlinelibrary.wiley.com/doi/10.1002/stem.495/full
Where do adult stem cells come from?
Adult stem cells receive much interest in the scientific community thanks to their ability to self-renew and generate numerous types of cells and tissues. There are two categories of stem cells: embryonic and adult.
Unlike embryonic stem cells, which have the ability to differentiate into more than one cell type, most adult stem cells are capable of forming only the types of tissue from which they originated. However, due to the controversy surrounding embryonic stem cell use, more and more researchers have turned their attention to the study of adult stem cells.
As a result, we now know of several adult tissues that serve as sources for stem cells. This is great news for people who suffer from degenerative conditions like osteoarthritis, muscular dystrophy and even Alzheimer’s disease.
The list of adult tissues known to contain stem cells keeps growing, and it includes bone marrow, brain tissue, peripheral blood and blood vessel tissue, skeletal muscle tissue, and liver and pancreas tissue.
Adult stem cells can be obtained from multiple tissues
Neural brain cells (NSCs) are multipotent cells that generate the central nervous system. They undergo asymmetric cell division, resulting in one non-specialized (blank) cell and one specialized cell. Japanese researchers have been able to use NSCs to replace dying neurons in lab mice . Currently there are numerous ongoing investigations into the response of NSCs in multiple sclerosis (MS) and Parkinson’s disease patients. The results may have future applications in the treatment of additional neurological conditions.
Hematopoietic stem cells (HSCs) are stem cells harvested from blood or bone marrow. They can differentiate into variety of specialized cells, such as white blood cells, which fight infection, and red blood cells, which carry hydrogen and platelets, and are responsible for blood clotting.
The downside of HSC stem cells is that their ratio in bone marrow is very low—1 in every 10,000-15,000 cells, which slows down the harvesting process considerably. Bone marrow also hosts skeletal stem cells (STCs), which give rise to osteoblasts (bone cells), cartilage and hematopoietic stroma.
An interesting niche of stem cells is found in the surface lining of the small and large intestines (ISCs). These stem cells divide continuously throughout life and are believed to be the source of most forms of cancer of the small intestine and colon. The longevity and renewal rates of ISCs becomes problematic in colorectal cancer, because they promote regeneration of the tumor after therapy.
In healthy adults, the liver is responsible for maintaining the balance between cell gain and cell loss. The liver’s impressive regenerative functions are attributed to hepatocytes, which are believed to be the adult stem cells of the liver. When the liver tears apart from virus infections, inflammation or is sectioned through hepatectomy, hepatocytes activate a stem cell-like behavior, giving rise to new tissue, replacing the lost liver cells.
Another important discovery has been made by Dr. Lola Reid of the University of North Carolina, an accredited expert in the research of liver development . As it turns out, the biliary tree, a network of vessels that connect the liver and pancreas to the intestine, generates a special type of adult stem cells, their major characteristic being pancreatic precursor cells, meaning they are destined to differentiate as pancreatic cells.
In a series of lab tests, these biliary cells have been manipulated to become islets, structures responsible for the production of insulin and c-peptide, a key component in the natural production of insulin. As a result, the blood sugar control in has been found to increased dramatically in lab mice. Dr. Reid hopes that her team’s efforts will speed up the process of finding a cure for diabetes.
Over the past few decades, scientific research has provided us with great insight on adult stem cells and their applications in regenerative medicine.
Unlike embryonic stem cells, adult stem cells can be isolated from a variety of adult tissue, including the brain, bone marrow, peripheral blood and even tumor-derived tissue cells, allowing scientists to avoid the ethical dilemma of using embryonic stem cells entirely. The risk of rejection with adult stem cells is considerably lower (the donor is usually the patient himself), and the differentiation rates are higher, providing much hope for future research to find cures for degenerative conditions in humans.
REFERENCES: MacKlis, Jeffrey D.; Magavi, Sanjay S.; Leavitt, Blair R. (2000). “Induction of neurogenesis in the neocortex of adult mice”. Nature 405 (6789): 951–5  Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-long Pancreatic Organogenesis – http://www.diabetesresearch.org/file/research-publications/2013-Stem-Cells_Biliary-Tree-Stem-Cells-to-Islets.pdf
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 .
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 .
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 .
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 .
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 .
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 . 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.
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 .
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 .
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 .
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 .
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.
 David King – Development and remodeling of skeletal tissue, School of Medicine, Southern Illinois University, 2009 http://www.siumed.edu/~dking2/ssb/skeleton.htm#development
 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