Exercise Triggers Muscle Stem Cells


New findings from researchers from the University of Illinois showed that adult stem cells in muscle are responsive to exercise. This discovery might provide a link between exercise and muscle health, and could provide the impetus for therapeutic techniques that use muscle-specific stem cells to heal injured muscles and prevent or restore muscle loss with age.

Mesenchymal stem cells (MSCs) in skeletal muscles have been known to be important for muscle repair in response to injury. Experiments that demonstrate the roles of mesenchymal stem cells in muscle repair have use chemical-induced injuries that initiate damage muscle tissue and inflammation. However, exercise also stresses muscle, and a research group led by kinesiology and community health professor Marni Boppart investigated whether MSCs also responded to exercise-induced stress.

According to Boppart, “Since exercise can induce some injury as part of the remodeling process following mechanical strain, we wondered if MSC accumulation was a natural response to exercise and whether these cells contributed to the beneficial regeneration and growth process that occurs post-exercise.”

Boppart’s group found that muscle-based MSCs respond to mechanical strain. In fact, mice subjected to vigorous exercise showed robust accumulation after exercise. They also found that MSCs do not directly contribute to new muscle fibers, but, instead, they release growth factors that spur other cells in muscle to fuse and generate new muscle.

Boppart’s research group isolated muscle-based MSCs after the mice exercised, and then they stained the MSCs with a fluorescent marker and injected them into other mice to see how they coordinated with other muscle-building cells. In addition to examining MSCs in vivo, Boppart’s laboratory examined the response of MSCs to strain on different substrates. They discovered that MSC response is very sensitive to the mechanical environment, indicating that conditions under which muscles are strained affects the activity of the cells.

Boppart added, “We’ve identified an adult stem cell in muscle that may provide the basis for muscle health with exercise and enhanced muscle healing with rehabilitation/movement therapy. The fact that MSCs in muscle have the potential to release high concentrations of growth factor into the circulatory system during exercise also makes us wonder if they provide a critical link between enhanced whole-body health and participation in routine physical activity.”

Since, preliminary data suggest MSCs become deficient in muscle with age; the group hopes to determine if these cells contribute to the decline in muscle mass over a person’s lifetime. The team hopes to develop a combinatorial therapy that utilizes molecular and stem-cell-based strategies to prevent age-related muscle loss.

Stem Cell Transplant into the Carotid Artery Shows Promise as Treatment for Traumatic Brain Injury


The injection of stem cells into the carotid artery of brain-injured rats allows the stem cells to move directly to the brain where they greatly enhance brain repair and healing, speeding functional neurological recovery.

This stem cell injection technique was combined with imaging to track the injected stem cells after their introduction into the animal. This study is part of a larger project to study the feasibility of stem cell treatments for traumatic brain injury (TBI) in humans. This research group is being led by Dr. Toshiya Osanai of Hokkaido University Graduate School of Medicine, Sapporo, Japan.

In this experiment, traumatic brain injuries were induced in laboratory rats, and seven days later, bone marrow stem cells were isolated and injected into the carotid arteries. Since injections directly into the brain are dangerous and can cause further brain damage, a technique that places stem cells into the peripheral circulation is preferable. However, many animal and clinical studies have shown that stem cells placed into the peripheral circulation tend to get stuck in the lungs, spleen, liver, and other places. For example, Wang W, et al Cell Transplant 2010;19(12):1599-1607 injected bone marrow mesenchymal stem cells into the heart of rats that had recently experienced a heart attack, and found the many of the injected stem cells stayed in the heart, but many others spread to the lungs, spleen, and lungs. This finding has been confirmed by several other studies as well (Zhang H, et al J Thorac Cardiovasc Surg. 2007;134(5):1234-40 & Wang W, et al, Regen Med. 2011;6(2):179-90). Therefore, Osanai’s research group decided to inject stem cells into the blood vessels that directly feed the brain. This way, the stem cells should find their way to the brain without getting lost in general circulation.

Before injection, the bone marrow stem cells were labeled with “quantum dots,” which are a biocompatible, fluorescent semiconductor created using nanotechnology. The quantum dots emit near-infrared light. Near-infrared light has very long wavelengths that penetrate bone and skin, which allowed the researchers to noninvasively monitor the stem cells for four weeks after transplantation.

Using this in vivo combination of optical imaging and carotid injection, Osanai and colleagues observed the bone marrow-derived stem cells enter the brain on the “first pass,” without entering general circulation. Within three hours, the stem cells began to migrate from the smallest brain blood vessels (capillaries) into the area of brain injury.

After four weeks, rats treated with stem cells showed significant recovery of motor function (movement), while untreated rats showed no such recovery. Examination of the treated brains confirmed that the stem cells had transformed into different types of brain cells and participated in healing of the injured brain area.

Stem cells from bone marrow are likely to become an important new treatment for patients with traumatic brain injuries and stroke. Bone marrow stem cells, like the ones used in this study, are a promising source of donor cells. However, despite the many questions that remain regarding the optimal timing, dose, and route of stem cell delivery.

In the new animal experiments, stem cell transplantation was performed one week after a traumatic brain injury, which is a “clinically relevant” time, since it takes at least that long to develop stem cells from bone marrow. Injecting such stem cells into the carotid artery is a relatively simple procedure that delivers the cells directly to the brain.

These experiments also add to the evidence that stem cell treatment can promote healing after traumatic brain injury, with significant recovery of function. Osanai and colleagues wrote that, with the use of in vivo optical imaging, “The present study was the first to successfully track donor cells that were intra-arterially transplanted into the brain of living animals over four weeks.”

Some similar form of imaging technology might be useful in monitoring the effects of stem cell transplantation in humans.  However, tracking stem cells in human patients will pose challenges, as the skull and scalp are much thicker in humans than in rats.  Clearly further studies are warranted to apply in vivo optical imaging clinically.

Low level laser treatment of bone marrow helps heal hearts after a heart attack


A fascinating paper published in the journal Lasers in Surgery and Medicine shows that low-level laser treatment of bone marrow can have profound effects on the ability of bone marrow stem cells to repair a heart after a heart attack.

The paper’s authors are H Tuby, L Maltz, and Uri Oron, who are members of the Zoology department at Tel-Aviv University, Tel-Aviv, Israel. The title of the paper is “Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart,” and it was published in the July edition of Lasers in Surgery and Medicine, 2001;43(5):401-109.

Oron and his co-workers have been studying the effects of photobiostimulation with low-level lasers on injured tissues. Their recent work established that application of low energy laser irradiation (LELI) to the site of injury in muscles, bone marrow or heart is beneficial. This irradiation does not heat the tissue and has not been found to cause adverse side effects.

The strategy of this study is rather simple: LELI on bone marrow stem cells after an laboratory animal has suffered a heart attack. The stimulated bone marrow stem cells might migrate to the injured heart and repair it. They used Sprague-Dawley rats, and induced heart attacks in those rats. Then they subjected the bone marrow of those rats to LELI 20 minutes or four hours after the heart attack. They also had rats that had not experienced heart attacks but were operated on as controls, and rats that had suffered heart attacks but were not treated with LELI. For those interested, they used a Ga-Al-As diode laser, power density 10 mW/cm², for 100 seconds.

The results were astounding. The size of the infarction was reduced by 75% and dilation of the ventricle was reduced 75% in those animals treated with LELI 20 minutes after the heart attack. There was also a 25-fold increase in the density of bone marrow-derived cells in the heart relative to the non-LELI-treated controls. This indicates that LELI offers a new approach to induce bone marrow stem cells to move into the blood stream, arrive at the damaged heart and repair it. This mobilization of bone marrow stem cells great shrinks the scar caused by a heart attack in laboratory animals. Maybe it’s time for trials in larger animals and then a phase I clinical trial in humans?

BrainStorm Announces that There Are No Dangerous Side Effects Observed in NurOwn Trial


A developer of innovative stem cell technologies, BrainStorm Cell Therapeutics Inc. has developed a stem cell treatment called NurOwn for central nervous system-based disorders. NurOwn™ is a product derived from human bone marrow mesenchymal stem cells. After these cells are collected from a patient by means of a bone marrow aspiration (which not nearly as invasive as a bone marrow biopsy), they are differentiated into nerve-like cells that can release the neurotransmitter dopamine and a nervous system-specific growth factor called glial-derived neurotrophic factor (GDNF). Dopamine cell damage and death is the hallmark of Parkinson’s Disease (PD), and GDNF-producing cells can protect healthy dopamine-producing cells and repair degenerated cells. This halts the progression of PD and other neurodegenerative diseases. BrainStorm’s NurOwn™ therapy for PD replaces degenerated dopamine-producing nerve cells and strengthens them with GDNF.

BrainStorm has just announced patient data from its ALS combined phase I & II human clinical trial. ALS patients who were treated with NurOwn, a stem cell-based product that BrainStorm had developed, did not show any significant side effects to the NurOwn treatment. Therefore, so far, NurOwn seems to be safe.

The leader of this clinical trial at Hadassah Medical Center, Prof. Dimitrios Karussis, stated, “There have been no significant side effects in the initial patients we have treated with BrainStorm’s NurOwn technology. In addition, even though we are conducting a safety trial, the early clinical follow-up of the patients treated with the stem cells shows indications of beneficial clinical effects, such as an improvement in breathing and swallowing ability as well as in muscular power. I am very excited about the safety results, as well as these indications of efficacy, we are seeing. This may represent the biggest hope in this field of degenerative diseases, like ALS.”

The Hadassah Medical Center ethics committee reviewed the safety data from the first four patients who were implanted with NurOwnTM, and concluded that the clinical trial should proceed with implanting the next group of ALS patients.

BrainStorm’s President, Chaim Lebovits, remarked: “We are happy to report that the first patients treated with our NurOwn technology did not present any significant side effects. This supports and strengthens our belief and trust in our technology. Based on the interim safety report, the hospital ethical and safety committee granted the company approval to proceed with treating the next patients. We are pleased with the progress we are making and look forward to continuing to demonstrate the safety of NurOwn in the future.”

This study is headed by Prof. Karussis, MD, PhD, head of Hadassah’s Multiple Sclerosis Center and a member of the International Steering Committees for Bone Marrow and Mesenchymal Stem Cells Transplantation in Multiple Sclerosis (MS), and a scientific team from BrainStorm headed by Prof. Eldad Melamed. This clinical trial is being conducted at Hadassah Medical Center in Israel in collaboration with BrainStorm and utilizes BrainStorm’s NurOwn technology for growing and modifying autologous adult human stem cells to treat ALS, which is often referred to as Lou Gehrig’s Disease. The initial phase of the study is designed to establish the safety of NurOwn, but will also be expanded later to assess efficacy of the treatment.