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 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 29, 2018 | Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Therapy
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
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.
by admin | Dec 17, 2018 | Aesthetics, Stem Cell Therapy
Researchers
have observed that the pH inside of certain stem cells affects their ability to
proliferate and differentiate. These cells include mesenchymal stem cells and
pluripotent stem cells, all of which have important applications in
regenerative medicine. It is therefore important that pH be optimized to ensure
that these stem cells can proliferate and differentiate so
that they can be as useful as possible when utilized for therapeutic purposes.
A recent review, published in Current Problems in Dermatology, explored the importance of pH to stem cell function as well as the factors that influence pH. According to the authors, a protein known as the sodium hydrogen exchanger regulates intracellular pH and impacts both the proliferation and differentiation of different types of stem cells. When pH is changed, either within the cell or outside the cell – where the cell is exposed to the change in pH – stem cell functions includingmaintenance, self-renewal, and pluripotency are altered.
The effect of pH in stem cells is highly relevant for skin conditions and therefore for the practice of dermatology. According to the reviewers, research on how the sodium hydrogen exchanger and pH levels affect skin stem cells (also known as epidermal stem cells) and their behavior could enable the discovery of new interventions to improve the use of stem cells in skin therapies. This research would be particularly relevant for skin conditions like melanoma, psoriasis, and wound healing because the movement and proliferation of stem cells are keyissues in these conditions.
Reference: Charruyer,
A. & Ghadially, R. (2018). Influence of pH on skin stem cells and their
differentiation. Current Problems in
Dermatology, 54, 71-78.
St. Petersburg, Florida
