Using Mesenchymal Stem Cells to Treat Cartilage Defects

Using Mesenchymal Stem Cells to Treat Cartilage Defects

Most large joints of the body contain cartilage, a substance that is softer and more flexible than bone. Because of its softness and flexibility, cartilage is well-suited to protect the bones as they move across one another. Unfortunately, this softness and flexibility also makes cartilage prone to injury and erosion. In patients with osteoarthritis, forexample, cartilage breaks down to the point that bone rubs against bone,causing pain and disability. Certain injuries can damage the cartilage (i.e.osteochondral lesion), which can essentially have the same effect.

Once the cartilage of joints has become damaged, there is little that can be done to fix it. Patients may receive steroid injections into the joint to reduce inflammation, and may rely on pain medications to relieve the pain and swelling. Short of joint replacement therapy, no treatments can reverse cartilage damage once it has occurred.

Fortunately, mesenchymal stem cells may soon be able to reverse cartilage defects that arise from osteochondral lesions and osteoarthritis. Wakitani and colleagues took samples of patients’ bone marrow, which contains mesenchymal stem cells. They then used various laboratory techniques to increase the number of stem cells in the sample. Four weekslater, the researchers then reinjected the concentrated stem cells back intothe same patient using their own source of stem cells. The Wakitani groupshowed that stem cell transplantation improved the patient’s clinical symptoms bysix months, a benefit that continued for two years on average. Samples takenfrom the patients 12 months later showed that the damaged cartilage had beenrepaired. In other work, Centeno and co-authors showed that bone marrow-derived mesenchymal stemcells could increase the volume of cartilage, reduce pain, and increase rangeof motion 24 weeks after stem cell transplantation.

Research continues to determine which stem cells are most useful, how many stem cells should be injected, how many injections need to be administered, and how should those stem cells be prepared before they are injected? Nonetheless, certain groups are making great strides in this area. In fact, the recent discovery of human skeletal stem cells promises to accelerate stem cell research into treating disorders of bone and cartilage.

Reference

Schmitt et al. (2012). Application of Stem Cells in Orthopedics. Stem Cells International. 2012: 394962

Stem Cell Secretomes for Brain Repair

Stem Cell Secretomes for Brain Repair

A number of different stem cell types have been shown to exert significant therapeutic effects when transplanted into the central nervous system. These cells include non-hematopoietic stem cells such as mesenchymal stem cells and neural/progenitor stem cells and carry out their effects by secreting what are known as neurotrophic paracrine factors, whichhelp to control the immune system.

In recent years, it has been suggested that rather than requiring the injection of stem cells, brain injury repair may be achieved by injecting the molecules that stem cells tend to secrete – known as secretome. The stem cell secretome includes growth factors as well as cytokines and chemokines. Investigators have begun to explore whether delivering these substances, rather than stem cells, could offer a more efficient means to therapy.

The rationale is that by delivering these substances directly, it should be possible to stimulate the proliferation of progenitor cells in the central nervous system and therefore instigate repair. However, initial studies have shown that the infusion of individual cytokines does not have the expected effect. According to the authors of a review published in Biochimie, it may be that multiple substances will need to be simultaneously infused in pre-tested concentrations so that they can act synergistically to optimize therapeutic effects.

Clinical trials are underway to determine the safety to patients of the secretome approach and to identify any relevant risks so that potential risks can be weighed against potential benefits of this type of therapeutic approach. There is also research on a wide variety of topics that will need clarification if effective stem cell secretome therapies are to be developed for brain repair. These topics include clarifying aspects of tissue transport and determining the mechanisms by which secretomes confer their benefits.

Reference: Drago, D. (2014). The stem cell secretome and its role in brain repair. Biochimie, 95(12), 2271-2285.

Parkinson’s Disease May Go Beyond Just Dopamine

Parkinson’s Disease May Go Beyond Just Dopamine

Parkinson’s disease is a progressive neurodegenerative disorder that causes tremor,rigidity, changes in facial expression, and several other symptoms. Whilesufferers usually retain their full cognitive abilities and memory, they tendto be impacted in mood and some mental health conditions that emerge as part ofthe condition process.

Parkinson’s disease is caused by loss of brain cells in a specific region of the brain called the substantia nigra. The neurons in this area of the brain contain dopamine, and as those nerve cells die, the levels of dopamine in the brain decrease. Consequently, patients with Parkinson’s disease often take medications that improve or accentuate dopamine signaling in the brain. These drugs can be effective for a certain period of time, but eventually, the condition will overcome the ability of these drugs to improve dopamine signaling. There is no cure for Parkinson’s disease, but researchers hope stem cells may be the answer.

Since dopamine drugs have worked reasonably well to control the symptoms of Parkinson’s disease, researchers assumed that replacing dopamine cells in the brain would help treat Parkinson’s disease. In a way, it did. When people with Parkinson’s disease received transplants of stem cells intended to produce dopamine, some of them experienced dramatic improvements in motor function. However, patients still had several other symptoms of Parkinson’s disease such as fatigue, bowel problems, sexual problems, and mood disorders. Neuroscience researchers realized Parkinson’s is not just about a loss of dopamine. It turns out, that while stem cells can help restore dopamine in people with Parkinson’s disease, they also coulduse help with serotoninneuron regenerating. 

As a result of this groundbreaking work, researchers are now planning and implementing experiments in which Parkinson’s disease patients will receive stem cell transplants containing both dopamine cells and seroton in cells. If effective, we will be one step closer to a new and powerful treatment for Parkinson’s disease.

Reference: https://blogs.scientificamerican.com/scicurious-brain/parkinsons-is-much-more-than-dopamine/?WT.mc_id=send-to-friend

Mesenchymal Stem Cells Improves Liver Function in Liver Failure

Mesenchymal Stem Cells Improves Liver Function in Liver Failure

Liver failure is a serious, potentially fatal condition in which large swaths of liver cells become dysfunctional and die. Liver failure is the result of several conditions including chronic alcohol consumption, exposure to drugs that are toxic to the liver (e.g. acetaminophen), autoimmune diseases, or infections such as hepatitis C. Liver failure causes several metabolic abnormalities including dangerously low levels of sodium, potassium, and phosphate in the blood. Moreover, four in 10 people with liver failure have trouble regulating their blood glucose levels, which can cause profound hypoglycemia. Since the liver detoxifies the blood, when the liver fails, patients can experience confusion from excessive amounts of ammonia and other substances in the blood. Seizures are also possible.

Short of liver transplantation, there are very few treatments for liver failure. Most treatments focus on restoring sodium, potassium, phosphate, and glucose levels in the blood, and bringing down ammonia levels. Fortunately, experiments show that human mesenchymal stem cells may be a promising treatment for liver failure.

Researchers enrolled 43 people with acute-on-chronic liver failure caused by hepatitis B infection. In this group, 24 patients were treated with mesenchymal stem cells derived from human umbilical cord and 19 patients received a saline solution. The groups received stem cells or placebo, respectively, three times every four weeks. Patients treated with mesenchymal stem cells showed better measures of liver function than those who received placebo. Livers of the patients treated with stem cells produced much more protein, albumin, and clotting factors, and were better able to process bilirubin. Importantly, no significant side effects were observed during the trial.

Given the serious nature of liver failure and the lack of effective treatments (besides liver transplant), this research is incredibly exciting. It offers hope that through further research scientists will be able to use mesenchymal stem cells to change the outcomes of people with acute-on-chronic liver failure.

 

Reference: https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.5966/sctm.2012-0034

Scientists Have Discovered Skeletal Stem Cells in Humans

Scientists Have Discovered Skeletal Stem Cells in Humans

The human skeleton is made up of bone, cartilage, fat, nerves, blood vessels, and bone marrow. While the skeleton is usually strong and vibrant in youth, it changes considerably with age. Many people, especially women, experience demineralization of bone called osteoporosis. Most of us will suffer from painful, stiff, arthritic joints either from osteoarthritis or rheumatoid arthritis or both. While some of the diseases of bone and joints have specific treatments, none of them helps to restore bone and joints to their younger state. If one could reintroduce skeletal stem cells into the body, that could all change. Excitingly, researchers have recently isolated human skeletal stem cells from bone and other tissues.

At first glance, this breakthrough may not seem so surprising. One might wonder: didn’t we already have stem cells that form bone and cartilage? The answer is yes, but with an important caveat. Before researchers recently isolated human skeletal stem cells, the only stem cells that could be used to produce bone and cartilage were rather unpredictable. In addition to bone and cartilage, the mesenchymal stem cells that have been long used to form these tissues could also produce fat, muscle, fiberglass, blood vessel cells, and other tissues. In other words, the stem cells were broadly multipotent and, by extension, could not easily be used for a specific purpose, like mending bone or repairing an arthritic joint. That is why the recent discovery of these particular skeletal stem cells is so important.

The researchers isolated skeletal stem cells from various human tissues, mainly bone. They then used the skeletal stem cells to regrow bone and/or cartilage. Not only did the stem cells produce bone and cartilage in the first animal they tested, but they could retrieve stem cells from that animal and then cause bone to regrow in a second animal. This means that the skeletal stem cells have the capability of reproducing themselves.

The same researchers also discovered that when a skeleton is injured, such as in a bone fracture, the number of skeletal stem cells in that area increases dramatically. This makes sense since these cells are used to repair and regrow bone. It is also a promising result because it suggests that stem cells could be used to accelerate bone and joint healing in humans.

Scientists not directly involved in this research heralded this finding as “an extremely important advance.” However, they also acknowledge that more work needs to be done before skeletal stem cells can be routinely used in patients with orthopedic conditions. Nevertheless, these results are an exciting development in the field of stem cell research and orthopedics.

 

Reference: https://www.sciencenews.org/article/humans-have-skeletal-stem-cells-help-bones-and-cartilage-grow

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