Protecting the Heart and Blood Vessels with Exosomes

Protecting the Heart and Blood Vessels with Exosomes

Heart disease is the leading cause of death in the United States, killing over half a million people every year. Heart disease encompasses several conditions and diseases, but the most common causes of deadly heart disease are a heart attack, heart rhythm problems, and heart valve problems. In each of these cases, damaged heart tissue becomes dysfunctional and the heart cannot pump blood efficiently or effectively. To combat this deadly set of diseases, researchers are searching for ways to heal and regenerate heart tissue. Stem cells and stem cell exosomes have shown promise.

While stem cells have been used in a variety of conditions, researchers long doubted the benefit of stem cells in heart disease. The heart, it was believed, was not a “hormonal” organ and thought to be relatively unresponsive to things like cytokines and other messengers. Fortunately, new research has completely changed this viewpoint. According to Drs. Sean Davidson, Kaloyan Takov, and Derek Yellon of the Hatter Cardiovascular Institute in the United Kingdom, “Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes.” The scientists go on to say that exosomes from stem cells “have been shown to be powerfully cardioprotective” and that exosomes produced by stem cells are capable of “activating cardioprotective pathways.”

In simpler terms, the heart and blood vessels are sensitive to the beneficial effects of exosomes. Thus, if exosomes are collected from stem cells, purified and concentrated, and then reinjected into the body, they can repair heart tissue. For example, exosomes collected from mesenchymal stem cells were able to reduce the amount of damage caused by a heart attack in mouse, and improve heart recovery after the event. This could have profound implications for humans who suffer a heart attack since damaged heart tissue can lead to heart failure, heart valve problems, and heart rhythm problems.

The study of stem cells and stem cell exosomes in heart disease is a relatively new science. Clinical trials will need to be performed to determine the role of exosomes in the treatment of heart disease. However, these findings represent an exciting avenue of research in the field of cardiology and regenerative medicine.

Stem Cell Exosomes Speed Up Muscle Regeneration

Stem Cell Exosomes Speed Up Muscle Regeneration

Muscle health and strength is an important determinant of a person’s ability to function in daily life. One of the major determinants of healthy aging is how well people retain their muscle mass. The more that skeletal muscle declines, the more likely someone would not be able to care for themselves independently. Injury to muscles whether through trauma, burns, or toxins can greatly interfere with a person’s ability to perform activities of daily living. While muscle cells have a limited ability to regenerate themselves, quite often, patients never regain their former strength and level of function after serious injury.

Stem cells would seem to be ideally suited to help in this regard. Since stem cells have the potential to become muscle cells, one could imagine infusing stem cells into an area of muscle damage or injury to restore overall muscle function. While this makes sense intuitively, it may not be the case. Stem cells, for example, form new muscle cells, but they do not form cells that participate in muscle function. And yet, stem cells are able to help muscles regrow into functional skeletal muscles.

How could stem cells promote skeletal muscle regeneration without becoming functional skeletal muscle cells? The answer, as it turns out, is that stem cells produce molecules that strongly promote muscle regeneration and muscle function.

Stem cells release these molecules in tiny packets called exosomes. Exosomes are tiny spheres that “bubble out” of stem cells, in a manner of speaking. Exosomes have a cell membrane, like cells themselves, but are much smaller, and they do not have the ability to reproduce. Instead, exosomes are highly packed with proteins, DNA, messenger RNA, micro RNA, cytokines, and other factors.

Nakamura and co-researchers showed exosomes can help regenerate muscle. These researchers showed that by injecting exosomes harvested from stem cells (without any of the stem cells themselves), they could increase muscle growth and blood vessel growth. In short, these molecules accelerate the rate at which muscles regenerate.

While more research is needed, this work suggests that exosomes retrieved from mesenchymal stem cells could be used to help regrow functional muscle in patients with various forms of muscle injury.

 

Reference: Nakamura et al. (2015). Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. FEBS Letters. 2015 May 8;589(11):1257-65.

Stem Cells Reverse Paralysis Caused by Spinal Cord Injury

Stem Cells Reverse Paralysis Caused by Spinal Cord Injury

Spinal cord injury can be one of the most devastating injuries. Long neurons that extend from the brain down the spinal cord are severed and scarred. In most cases, this damage can never be repaired. If patients survive an injury to the spinal cord, they can be permanently paralyzed. Researchers have attempted to use high-dose steroids and surgery to preserve the spinal cord, but these approaches are either controversial or largely ineffective.

Ideally, one would create an environment in which nerve cells in the spinal cord could regrow and take up their old tasks of sensation and movement. One of the most promising approaches to do just this is stem cell transplantation.

To test this concept, researchers used stem cells derived from human placenta-derived mesenchymal stem cell tissue (not embryonic stem cells) to form neural stem cells in the laboratory. These neural stem cells have the ability to become neuron-like cells, similar to those found in the spinal cord. The researchers then used these stem cells to treat rats that had experimental spinal cord injury. The results were impressive.

Rats treated with neural stem cells regained the partial ability to use their hindlimbs within one week after treatment. By three weeks after treatment, injured rats had regained substantial use of their hindlimbs. The researchers confirmed that this improvement was due to neuron growth by using various specialized tests (e.g. electrophysiology, histopathology). Rats that did not receive stem cells did not regain substantial use of their hindlimbs at any point in the study.

This work is particularly exciting because it shows that stem cells can restore movement to animals who were paralyzed after spinal cord injury. Moreover, the researchers used human stem cells derived from placenta, which suggests that this effect could be useful in human spinal cord injury patients (perhaps even more so than in rats). While additional work is needed, these results offer hope to those who may one day develop severe spinal cord injury.

Reference:

Zhi et al. (2014). Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury. Neural Regen Research, 9(24): 2197–2204.

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.

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