Using Exosomes to Treat Kidney Diseases: State of the Research

Using Exosomes to Treat Kidney Diseases: State of the Research

Kidney diseases are among the most expensive and most debilitating diseases. Total costs are in excess of $50 billion a year, with $30 billion spent on people with end-stage renal disease including hemodialysis and kidney transplantation. People with kidney diseases have diminished quality of life, and substantial amounts of their time are devoted to medical treatment. Not surprisingly, researchers are aggressively pursuing novel therapies to treat kidney diseases before they result in end-stage renal disease. Stem cells and exosomes are among the most exciting and the most promising research topics in this area.

Most cells release tiny packets called extracellular vesicles. The most notable extracellular vesicles are exosomes. While small, exosomes are filled with high concentrations of potentially helpful substances such as RNA, DNA, and proteins. While most cells release exosomes, researchers are particularly interested in exosomes released by stem cells. It is within these exosomes that stem cells pass along the substances that make stem cells helpful in tissue repair and regeneration.

Zhang and coauthors reviewed the recent advances that have been made using exosomes to treat kidney diseases. Most of the work has focused on acute kidney injury or AKI.  Acute kidney injury can lead to chronic kidney disease and kidney failure. Thus, if one could stop AKI, they could potentially reduce the risk of chronic kidney disease.

Many different research groups have shown the power of exosomes and other extracellular vesicles in treating acute kidney injury. Exosomes taken from mesenchymal stem cells protected kidney cells from cell death and fibrosis and helped them repair themselves. The same was true of exosomes derived human umbilical cord stem cells. Even stem cells taken from human liver cells were able to improve kidney function after injury. There are many other examples.

Gatti et al. reported that extracellular vesicles derived from human adult mesenchymal stem cells could protect against acute kidney injury, but, most impressively, also halted the progression of AKI to chronic kidney disease. This finding has important implications for people who suffer from serious acute kidney illnesses, such as kidney ischemia. It means that—if confirmed in human studies—stem cell-derived extracellular vesicles can help treat kidney disease in the short term and reduce the risk of that illness becoming a chronic, debilitating problem.

Further research is needed in this field but, initial results confirmed by many laboratories have created well-founded enthusiasm for the future.

Reference: Zhang, W. et al. (2016). Extracellular vesicles in diagnosis and therapy of kidney diseases. American Journal of Physiology – Renal Physiology. 2016, Nov 1; 311(5): F844-F851.

Treating Chronic Pain with Mesenchymal Stem Cells

Treating Chronic Pain with Mesenchymal Stem Cells

Chronic pain, that is, pain lasting for more than 12 weeks, is extremely common. As many as 1 in 3 Americans struggle with chronic pain, making it perhaps the most common physical condition that afflicts humans. Chronic pain is a source of significant suffering; it makes daily tasks more difficult, limits people’s ability to do the things they enjoy, and greatly diminishes the quality of life.

Perhaps the most frustrating aspect of chronic pain is that there are usually no good treatments. Because the pain is chronic, patients who try to treat chronic pain with medications must take drugs every day. Acetaminophen and non-steroidal anti-inflammatories (NSAIDs) like ibuprofen can help take away some suffering, but they are usually only partially effective. Opioids are stronger, of course, but have such a high risk of causing dependence and addiction that few doctors will prescribe for chronic non-cancer pain. Physical therapy helps some, but not most people. Surgery may be able to treat people with certain types of chronic musculoskeletal pain; however, orthopedic surgery is a major ordeal with no guarantees of success. Consequently, most people with chronic pain are left with very few treatment options.

Perhaps this lack of chronic pain treatment options is what makes recent stem cell research in chronic pain treatment so exciting. Researchers are learning that mesenchymal stem cells appear to be able to treat people with chronic pain. For example, in a study of patients with low back pain who received treatment autologous stem cells (their own stem cell populations purified, expanded, and re-injected in their bodies), their pain and disability decreased to the same levels as people who underwent major orthopedic surgery (spinal fusion or total disc replacement). Another lab in Japan showed similar results.

The same benefit may occur in knee arthritis (osteoarthritis), as well. Researchers showed that autologous stem cells were able to increase the size of the knee meniscus cartilage in a patient with severe knee arthritis. It should be noted that damaged knee meniscus cartilage is one of the main sources of chronic pain in knee osteoarthritis.

Of course, the number of patients treated in these studies is relatively small. Larger studies will be required to confirm that mesenchymal stem cells can treat chronic pain. However, these results are intriguing, since a staggering number of studies show autologous stem cell treatment to be safe. Indeed, mesenchymal stem cell treatment is now widely available in clinics and medical practices.

Reference: Waterman R. et al. (2011). Treating Chronic Pain with Mesenchymal Stem Cells: A Therapeutic Approach Worthy of Continued Investigation. Journal of Stem Cell Research & Therapy. 2011, S2 DOI: 10.4172/2157-7633.S2-001.

Bringing Autologous Stem Cell Treatments to the Elderly

Bringing Autologous Stem Cell Treatments to the Elderly

Autologous stem cell treatments offer several advantages over other forms of stem cell treatment. In autologous stem cell treatment, a patient’s own stem cells are retrieved, processed, and injected back into the patient’s body. There is no need for a stem cell donor, and the entire procedure can take place in the same medical office. Since the patient’s own cells are used for an autologous stem cell treatment, there is no risk of disease transmission from a donor (because there is no donor) and no risk of rejection (because they are the patient’s own stem cells).

Unfortunately, younger stem cells are better for regenerative medicine than older stem cells are. Moreover, older people have fewer stem cells that can be harvested than they did when they were younger. So while autologous stem cell treatment is still advantageous, it becomes more difficult to achieve as patients get older because their stem cells are fewer and less potent. Making matters worse, older stem cells compete against more youthful stem cells, making autologous stem cell treatments potentially even less effective in older patients.

Fortunately, stem cell researchers are coming up with ways to make the most out of the stem cells that older patients still have. They still take a sample of tissue, such as fat, and harvest the stem cells contained within it. However, instead of injecting all stem cells from the sample (both older and youthful stem cells), researchers select and use only youthful stem cells. Furthermore, they make the treatments even more effective by injecting other substances (e.g. extracellular matrix) that help youthful stem cells survive, grow, and thrive.

To demonstrate the effectiveness of their approach, researchers collected mesenchymal stem cells from about a dozen older individuals aged 65 to 86 years old. They then assorted the stem cells into different groups, separating youthful from older stem cells. They then used special factors to help the youthful stem cells grow, increasing the numbers by an impressive 17,000 times. So while only 8% of stem cells produced by older individuals are “youthful,” this laboratory process increased those numbers to a point that they can be used for stem cell treatments—even stored for future use!

The next phase of the research will be to inject these youthful stem cells into older patients and assess their effectiveness. However, even these preliminary results are exciting because they suggest that people of all ages can potentially benefit from autologous stem cell treatments, not just middle age and younger individuals.

Reference: Block, TJ et al. (2017). Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies. Stem Cell Research & Therapy. 2017 Oct 27;8(1):239.

Mesenchymal Stem Cell Treatment for ALS is Apparently Safe and Feasible

Mesenchymal Stem Cell Treatment for ALS is Apparently Safe and Feasible

Amyotrophic lateral sclerosis or ALS is a devastating, progressive neurological disease. While the precise cause is unknown, ALS does destroy nerve cells in the spinal cord, which causes several debilitating symptoms. Often the first symptom of ALS is weakness in the hands or arms that is usually more pronounced on one side of the body. As more spinal cord nerve cells become dysfunctional and die, patients with ALS become weaker, their movements grow slower, and their muscles begin to atrophy (i.e. break down). At the same time, some muscles in the limbs become spastic, which means they are constantly in a contracted state. In later stages of ALS, patients have difficulty swallowing and breathing.

The only drug to have any known survival benefit in ALS is riluzole. Patients who take riluzole live longer than those who do not; however, the drug does not improve function or meaningfully reduce symptoms. The only other approved ALS treatment, edaravone, may slow the rate at which ALS gets worse. However, neither of these drugs is a cure—far from it, in fact. Indeed, doctors and patients are left with virtually no effective treatment options for ALS.

Because ALS is caused by the destruction of nerve cells in the spinal cord, the regenerative properties of stem cells may offer a solution. The hypothesis is that stem cells—and exosomes collected from stem cells—can help protect, preserve, or even regenerate cells that are affected by ALS.

A flurry of research has been published over the last decade documenting the safety and possible effectiveness of mesenchymal stem cells for the treatment of ALS. In 2009, Deda et al. showed bone marrow stem cells injected into the spinal area were safe in patients with ALS, even showing that some patients had improvements in neuromuscular testing. The research groups of Karussis, Mazzini, Blanquer, and Baek showed similar safety results. Martinez et al. showed that stem cells derived from bone marrow could improve survival in patients with ALS. Rushkevich et al. showed that stem cell infusion improved the quality of life in patients with ALS.

While more work is clearly needed to determine the full effectiveness of stem cell treatment for ALS, the number of researchers working on this topic and the number of successful studies published in this area are reasons for hope. These clinical studies show that stem cell treatment for ALS is clearly safe and feasible. What is needed are larger clinical trials that specifically focus on the effectiveness of treatment, both in the near- and long-term.

Reference: Roberta Bonafede and Raffaella Mariotti. (2017). Stem cell mobilizers: ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. Frontiers in Cellular Neuroscience. 2017; 11:80.

Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Promising Data for the Use of Stem Cells to Treat Perianal Crohn’s Disease is Accumulating

Crohn’s disease, a form of chronic inflammatory bowel disease, affects an estimated 700,000 people in the United States, affecting men and women equally. While the disease is characterized by abnormal inflammation in the gastrointestinal and digestive tracts, some people with the illness develop perianal Crohn’s disease. In this case, the inflammation extends to areas around the anus. The precise proportion of Crohn’s disease patients who develop perianal Crohn’s disease is debated, but the need for better treatments for the condition is not.

Unfortunately, though there are several drug and surgical interventions that have been developed to treat perianal Crohn’s disease, each of the available treatment options suffers critical limitations, including risks for adverse side effects.  There is no available therapeutic approach that successfully achieves long-term remission.

Based on the need for – and lack of – more efficacious interventions for perianal Crohn’s disease and the ability of cell-based therapies to address similar types of disease, researchers have positioned that stem cell therapy may be a promising avenue for the relevant patient population. A recent review published in the Journal of Crohn’s and Colitis covers the research that has been conducted to address this possibility and the data that suggest that mesenchymal stem cells could provide a safe and effective way to treat perianal Crohn’s disease without the unwanted side effects associated with conventional treatment options.

In this review, the authors cover clinical trials on cell-based therapies for perianal Crohn’s disease, including phase 1, phase 2, and phase 3 randomized controlled trials. The authors consider the differences in outcomes between conventional treatments and cell-based therapies and offer suggestions for the direction of research into the use of stem cells for the treatment of perianal Crohn’s disease.

 

 

Reference: Lightner, A.L. & Faubion, W.A. (2017). Mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: What we have accomplished and what we still need to. Journal of Crohn’s and Colitis, 11(10), 1267-1276.

How Stem Cells May Help Those with Chronic Pain

How Stem Cells May Help Those with Chronic Pain

A review in the Journal of Stem Cell Research & Therapy has summarized an array of studies that demonstrate that a specific type of stem cell – the mesenchymal stem cell – may be beneficial as a therapeutic approach to chronic pain. The authors point to the huge burden of chronic pain. It is estimated that more than 115 people suffer from the condition, which is more than those who suffer from diabetes, stroke, cancer, and coronary heart disease combined.

Chronic pain is also associated with significant losses in productivity. Given how extreme the burden of chronic pain has become, the National Institute of Medicine has suggested that finding effective ways to alleviate chronic pain should become a priority for the nation.

Regenerative medicine has offered an effective way to treat a variety of injuries and diseases, including some that are related to chronic pain. As the term “regenerative medicine” implies, much of the research into the clinical effects of stem cells have shown that they lead to beneficial outcomes by regenerating damaged tissue by replacing that tissue with new cells.

This new review looks at the potential of mesenchymal stem cells to specifically improve chronic pain through the ability of the cells to suppress inflammation. Given that inflammation is a common characteristic of conditions associated with chronic pain, a strategy that addresses this phenomenon could represent an effective way to help those with chronic pain that comes from things like degenerative disc disease and osteoarthritis.

The current approaches to chronic pain are limited in their ability to reduce or control pain, so there is a great need to develop more effective therapies. Research thus far into the potential impact of mesenchymal stem cells on chronic pain has provided promising results regarding effectiveness and safety. Specifically, these stem cells have not been associated with adverse side effects, they lead to the development and growth of healthy tissue, and they appear to provide pain relief. Future research will help to clarify the mechanisms by which mesenchymal stem cells may confer their benefits to those with chronic pain and provide new insights into how can best use these cells to help chronic pain sufferers.

 

 

Reference: Waterman, R.S. & Betancourt, A.M. (2011). Treating chronic pain with mesenchymal stem cells: A therapeutic approach worthy of continued investigation. Journal of Stem Cell Research & Therapy, S2, 1-5.

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