by admin | Jan 27, 2019 | Exosomes, Heart Failure, Kidney Disease, Stem Cell Research, Stem Cell Therapy, Stroke, Umbilical Stem Cell
Tissue injury is common to many human diseases. Cirrhosis results in damaged, fibrotic liver tissue. Idiopathic pulmonary fibrosis and related lung diseases cause damage to lung tissue. A heart attack damages heart tissue, just as a stroke damages brain tissue. In some cases, such as minor tissue injury, the damaged tissue can repair itself. Over time, however, tissue damage becomes too great and the organ itself can fail. For example, long-standing cirrhosis can cause liver failure.
One area of active research is to find ways to protect tissue from injury or, if an injury occurs, to help the tissue repair itself before the damage becomes permanent and irreversible. Indeed, tissue repair is one of the main focuses of regenerative medicine. Likewise, one of the most promising approaches in the field of regenerative medicine is stem cell therapy. Researchers are learning that when it comes to protecting against tissue injury and promoting tissue repair, exosomes harvested from stem cells are perhaps the most attractive potential therapeutic.
Why are stem cell exosomes so promising? Exosomes are small packets of molecules that stem cells release to help the cells around them grow and flourish. While one could inject stem cells as a treatment for diseases (and they certainly do work for that purpose) it may be more effective in some cases to inject exosomes directly. So instead of relying on the stem cells to produce exosomes once they are injected into the body, stem cells can create substantial amounts of exosomes in the laboratory. Exosomes with desired properties could be concentrated and safely injected in large quantities, resulting in a potentially more potent treatment for the disease.
Indeed, researchers have shown that extracellular vesicles (exosomes and their cousins, microvesicles) can be collected from stem cells and used to treat a variety of tissue injuries in laboratory animals.
Just a few examples of this research:
- Exosomes from umbilical cord-derived mesenchymal stem cells were able to accelerate skin damage repair in rats who had suffered skin burns.
- Exosomes from the same type of stem cell protected the lungs and reduced lung blood pressure in mice with pulmonary hypertension.
- Exosomes from endothelial progenitor cells protected the kidney from damage caused by a lack of blood flow to the organ.
In this growing field of Regenerative Medicine, research is constant and building as new science evolves from stem cell studies. Researchers are closing in on the specific exosomes that may be helpful in treating human diseases caused by tissue injury.
Reference: Zhang et al. (2016). Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. International Journal of Molecular Sciences. 2016 Feb; 17(2): 174.
by admin | Jan 25, 2019 | Exosomes, Stem Cell Research
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.
by admin | Jan 15, 2019 | Exosomes, Mesenchymal Stem Cells, Stem Cell Research, Studies
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.
by admin | Jan 14, 2019 | Stem Cell Research, Stem Cell Therapy, Stroke
Patients who suffer ischemic stroke have some treatment
options, but many of them require immediate intervention and so are not useful
if too much time has elapsed between the stroke and treatment. Therapies that
employ stem cells are promising alternatives because stem cells can differentiate
into brain cells and potentially help to replace tissue that has been damaged
or destroyed.
A recent study published in Stem Cells
and Development has shown for the first time that a specific type of stem
cell – called ischemia-induced multipotent stem cells – may be able to help
with such repair of brain tissue in patients who have suffered a stroke.
Specifically, the research team demonstrated the technical ability to isolate
the ischemia-induced multipotent stem cells from the brains of elderly stroke
patients.
The scientists then used protein
binding techniques to determine where in the brain these stem cells came from.
They found that the cells came from areas of the brain where brain cells had been
damaged or killed from the stroke. These cells were located near blood vessels
and expressed certain biological markers that enabled the researchers to
confirm that they qualified as stem cells. Specifically, these cells had
proliferative qualities that suggested that they could potentially be used to
re-populate damaged areas of the brain. The cells also showed the ability to
differentiate into different types of cells, a key characteristic of stem cells
used for therapeutic purposes.
This study represents a
significant step in overcoming the technical challenges associated with
isolating and classifying ischemia-induced multipotent stem cells. The next
step for researchers will be to test the potential of these cells in stroke
treatment. If researchers show that these stem cells can be used to
successfully repair damaged areas of the brain – and more importantly, restore
functions that were disrupted by the stroke – then physicians and scientists
may be able to work together to translate these findings into therapies that
are regularly used in stroke.
Reference
Tatebayashi et al. 2017. Identification of multipotent stem
cells in human brain tissue following stroke. Stem Cells and Development, 26(11), 787-797.
by admin | Jan 4, 2019 | Stem Cell Research, Stem Cell Therapy, Studies
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.
by admin | Dec 27, 2018 | Stem Cell Research, Stem Cell Therapy
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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