In this paper I will mainly focus on the effects of stem cell injections on skeletal muscle injures in mice, this is because those types of muscle injuries are extremely common. Skeletal muscle is a highly specialized tissue made up of non-dividing, multi-nucleated muscle fibers, which contract to generate force in a controlled and controlled manner,which account for up to half the mass of the human body. However, effective muscle function is both mechanically and energetically demanding, making this tissue particularly susceptible to damage. Such muscle damage may reduce mobility and contribute to metabolic. Skeletal muscle has a strong innate tissue damage repair capability. Despite the proficiency of this intrinsic repair capability, severe injuries resulting in a significant loss of muscle tissue overwhelm the innate repair process and require intervention in order to restore muscle function. Natural muscle damage repair is a step – wise process requiring the coordinated activity of a number of cell types involving three healing steps: degeneration and inflammation, regeneration and fibrosis. There is a phase of myofiber degeneration immediately after injury that is initiated by the release of proteases into the tissue stroma; these proteases automatically digest myofibers and thereby release tissue debris along the injury zone.
In addition, macrophages stimulate the paracrine release by T – cells of cytokines and other chemotactic factors that can recruit progenitor and satellite cells with muscle regeneration capacity locally. While the degeneration phase is transient, the subsequent regeneration phase of myofibers is the first step in the long-term pattern of skeletal muscle injury. This phase may begin as early as 24 hours after injury, as evidenced by the cytokine-mediated induction of local satellite cells that previously lie dormant between the basal lamina and sarcolemma; however, the complete formation of new, centronucleated myofibers cannot be detected histologically until at least 3 – 5 days after injury. It is likely that the differentiation of satellite cells into myotubules and myofibers is a crucial event in the regeneration phase. To date, these progenitor cells are perhaps the best characterized and are often referred to as ” muscle stem cells ” because they favor myogenic lines. Fibrous tissue prevents the full recovery of the muscle and current therapies fail to achieve total recovery of the muscle. Gene and (or both) cell therapy are potential future treatments for serious muscle injuries. The properties of stem cells related to growth factors and /or cytokines can improve muscle healing and allow for long – term recovery. Perhaps the biggest limitation for patients resulting from skeletal muscle injury pathophysiology is the formation of a dense fibrotic scar tissue.
Clearly, fibrosis is caused by a deleterious increase in the cytokine growth factor (TGF)-B1 following injury. MDSCs and other myogenic cells differentiate into myofibroblasts, which produce collagen type I, the main component of fibrotic tissue, in the presence of this cytokine. Fibrosis can ultimately prevent patients from returning to their basic function, partly by preventing the formation of new axons towards myofibers, and contributes to a decrease in muscle contractility and range of movement. It is a known fact that as we get older, our cells gradually lose the ability to heal themselves and injury can cause muscle loss due to a process called muscular atrophy, which is where regenerative medicine takes place. Like stem cell injections, which fall under the category of stem cell therapy to treat or prevent a disease or condition by using stem cells. Stem cells are capable of differentiating into specific types of cells. The two defining features of a stem cell are perpetual self-regeneration and the ability to differentiate into a specialized type of adult cell. There are two main classes of stem cells: pluripotent cells that can become any cell in the adult body and multipotent cells that are limited to a smaller cell population. In the case of muscle damage, the cells that have been used most frequently in pre-clinical trials are muscle satellite cells (MSCs).
MSCs have the ability to renew and differentiate into multiple lineages of connective tissue, including bone, fat, cartilage, tendon, muscle, and bone marrow stromal cells. Stem cell injections has proven to be successful in injured/aging mice but do to some challenges this form of therapy has not move forward to clinical trials, but results may forecast a promising future for regenerative medicine Research The research I found was limited to animal models and majority of the studies were performed in laboratory experiments on mice. For example, researchers at the Georgia Institute of Technology have developed a molecular matrix, a hydrogel, to deliver muscle satellite cells (MSCs) directly to damage muscle tissue in patients whose muscles do not regenerate well. The hydrogel was successfully in delivering MuSCs to injured, aged muscle tissue in mice and boosted the healing process while protecting the stem cells from harsh immune reactions. CS In Addition, the same method was also successful in mice with a muscle tissue deficiency that matched Duchene muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease. Researchers at the University of Colorado in Boulder and the University of Washington also discovered that stem cells injected into the muscles of the mouse led to an increase for the rest of the mouse’s life.
The injuries not only healed, but muscle mass increased by 50 percent and muscle volume increased by 170 percent. For some reason, the stem cells did not simply multiply and replace old damaged cells. They formed new connections to myofibers and increased significantly in numbers within the muscle. In other words, whatever the transplanted stem cells did, it was much more than just repairing damage and normalizing things. Issues with Research When it comes to stem cell injections moving into clinical trials there are a few challenges that need to be faced for that to happen. For example our immune system, researchers at the Georgia institute for technology found that simply injecting additional muscle satellite cells into damaged, inflamed tissue was inefficient because the new cells enter the body when the immune system on the warpath. And like any muscle injury or disease its going to attract the immune system and where as in any other case this would be a good thing, in the case of aged or dystrophic muscles it is not. This is because in this case the immune system release toxins that kill the stem cells off, in fact when tested the found that between and 1 and 20 percent of the injected MSCs actually made it to the targeted site and those that did were weakened. Which is why they developed a solution to coat the cells in , a hydrogel often start out as water-based solutions of molecular components that resemble crosses, and other components that make the ends of the crosses attach to each other.
When the components come together, they fuse into molecular nets suspended in water, resulting in a material with the consistency of a gel. If stem cells or a drug are mixed into the solution, when the net, or matrix, forms, it ensnares the treatment for delivery and protects the payload from death or dissipation in the body. Whereas researchers at the University of Colorado at Boulder and the University of Washington ran into a different issue/ concern. The mice used in this experiment injuries were inflicted directly using barium chloride injections and its made the question if that was a natural injury or muscle loss due to a disease would the stem cell reaction be similar. And they also questioned if age at the time of injury/ treatment played a major role in the effects since they used mice that were about 3 months in age for the treatment and as donors. Sine the muscles in mice are very small so it’s unclear on how well the cells would migrate in the larger muscles of humans. Similarities Mouse models are regarded as the most advanced and practical models used as an alternative to genetic research in humans. Ethical concerns in many cases prevent scientists from using human subjects and embryos to test stem cell therapies that could be used for future use.
In such cases, it can be extremely useful that an impressive 99 percent of the genes belonging to mouse DNA match the corresponding human counterpart gene sequences. In this way, scientists can use embryonic and adult stem cells from mice and conduct their research unhindered while also gaining important insights into the potentially practical adaptation of research to clinical trials in humans. Mouse studies make stem cell research more bright than ever before. Many of the past few achievements and advances in embryonic stem cell research have been achieved using ES cells grown from different mouse models. Since embryonic cells can play a role in virtually any other cell type, mouse ES cells have already been used to develop and study different mouse tissue samples closely resembling human tissue and to evaluate their reaction to certain treatments and stimuli. The genetic manipulation of ES cells in the mouse and the addition of human genetic material are also at the forefront of embryonic stem cell research.
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