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Heart disease cure with ardiosphere derived stem cell?

Heart diseases has become the number one killer in western countries. Cardiosphere derived stem cell are already a promising therapeutic treatment for cardiomyopathy. At the same time current treatments for human ischaemic dilated cardiomyopathy is still done with drug regimen or invasive implantable devices. While studies on rodents show initial proof of concept. Translating cardiosphere derived stem cell therapy to humans is still not done.

Cardiosphere derived stem cell used in animal model

To change this mind set researchers are using large animal studies, to proof safety of stem cells therapy for human ischaemic dilated cardiomyopathy. Interestingly, in the wild animal kingdom naturally occurring cardiomyopathy of humans cannot be found and studied in the laboratory. However, naturally occurring cardiomyopathy does affect the well-being of domestic dogs. For a Doberman pinschers, ischaemic dilated cardiomyopathy also appears to be a major cause of death.

Researchers decide to use the Doberman pinschers with ischaemic dilated cardiomyopathy as a large animal model of cardiomyopathy. To translate safety of human adult stem cell therapy for heart diseases.

Researchers infused dog stem cells into the coronary vessels of Doberman pinscher ischaemic dilated cardiomyopathy. Adverse events were checked, and cardiac functions were measured. Researchers reported that no adverse events occurred during and after cell infusion. After natural deaths the dog hearts showed no sign of immune rejection from the transplanted stem cells.

An other stem cell with promising prospects.

Even though cardiosphere derived stem cells are a promising treatment option, according to most researchers Mesenchymal stem cells (MSCs) have the greatest potential for use in human heart diseases. Mesenchymal stem cells are easily harvetesed from the umbilical cord or from bone marrow (less easy). The therapeutic potential of Mesenchymal stem cells in heart diseases is based on the ability of Mesenchymal stem cells to differentiate into cardiac tissue. But, one of the major problems for clinical application is the harsh environment resulting in high cell death of the transplanted mesenchymal stem cells. Researcher are therefore looking for solutions like modifing mesenchymal stem cells for cardiac regeneration.

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Neurodevelopment and cerebral palsy in preterm births

Nearly 10% of all births are preterm births. Even though the survival of preterm babies has improved over the past several decades. Prematurity still accounts for up to 70% of perinatal deaths and if a baby survives problems with neurodevelopment and cerebral palsy often occur.

The complications of preterm infants are caused by inflammation affecting the placenta and its membranes termed chorioamnionitis. Chorioamnionitis and preterm birth are strongly linked.
Chorioamnionitis is believed to be the major cause of preterm birth and brain injury. Damage by bacteria on the chorion, amnion, and/or the placenta, can lead to a fetal inflammatory response. The bacterial infections have adverse consequences for the developing fetal brain.

Current research

According to recent research, there is a strong causal link between chorioamnionitis, and severe postnatal neurological deficits and cerebral palsy. At the moment there are no clinical treatments to repair brain injury in preterm babies born after pregnancy compromised by bacterial infection. There is a need for a treatment and at the moment the most promising treatments are therapeutic intervention with stem cells. Many clinical trials are starting to investigate the efficacy of stem cells to treat patients with cerebral palsy. Stem cells, obtained from umbilical cord tissue and cord blood. Which normally thrown away after after birth, are becoming a safe and effective therapy.

At the moment It is unknown which stem cell type(s) are the most best for administration to preterm babies to treat brain demage. Different stem cell populations found in umbilicalcord, such as mesenchymal stem cells and endothelial progenitor cells / hematopoietic stem cells. They have a number of benefits that may target preterm brain damage caused by chorioamnionitis. Mesenchymal stem cells have strong immunomodulatory cabiblities. Protecting against neuroinflammatory processes triggered during infection to the fetus. Hematopotic stem cells have vascular reparative qualities that make them ideal for neurovascular repair.

A promising therapy is to combine Mesenchymal stem cells with endothelial progenitor cells /hematopoietic stem cells to target inflammation and promote vascular reparation.

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The race to make the first artificial tooth from stem cells (tooth regeneration)

Stem Cells from Dental pulp can specialize in different types of tissues and cells. The multipotency of Stem Cells from Dental pulp are often compared with mesenchymal stem cells from the umbilical cord and stem cells from bone marrow. Compared with stem cells from bone marrow it has been demonstrated that availability, and proliferation of bone marrow stem cells are less greater than stem cells from Dental pulp. Like stem cells from the umbilical cord, stem cells from dental pulp are also capable to regenerate cornea, nerves, renal tissues, bladder, skeletal, lung tissue, muscles. They also have demonstrated good neurogenic and angiogenic potential.

Tooth Regeneration

Suji T and his team formed a fully functional mouse tooth by combining isolated dental epithelial and mesenchymal stem cells [1]. They also reported that they transplanted succfully a tooth into a toothless mouse [3]. Angelova Volponi and her team also reported to have made a mature teeth with dentin and enamel in an animal model [2]. Even tough scientist seem to have regenerated an artificial tooth in animals, they still have not reported a complete regenerated human tooth. Only a few human studies have been executed till date. Although scientist have been able to regenerate bone, periodontal tissue and pulp tissue. They still haven’t been able to regenerate tissues that completely resemble tissues in their natural form.

One day a regenerated tooth will be made and will be commercially available. The future of stem cell therapy in dental applications looks promising. But safety concerns of stem cell therapy needs to be fully established before it can be used in humans. Ongoing research is needed and understanding signalling molecules, gene expression and proteomics of stem cells is important. It is the future directions that will take us a step forward to successful regeneration of tooth.

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[1] Ikeda, R., Morita, K., Nakao, K., Ishida, K., Nakamura, T., Takano-Yamamoto, T., et al. (2009) Fully Functional Bioengineered Tooth Replacement as an Organ Re- placement Therapy. Proceedings of the National Academy of Sciences, 106, 13475-13480.
[3] Angelova, V.A., Kawasaki, M. and Sharpe, P.T. (2013) Adult Human Gingival Epi- thelial Cells as a Source for Whole-Tooth Bioengineering. Journal of Dental Re- search, 92, 329-334.
[2] Oshima, M., Mizuno, M., Imamura, A., Ogawa, M., Yasukawa, M., Yamazaki, H., et al. (2011) Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy. PLoS ONE, 6, e21531.

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Mesenchymal Stem Cells from umbilical cord used in skin transplants

When a patient needs new skin. Doctors and researchers typically grow excess skin on other parts of their bodies – a process that can take months. A new technique uses stem cells derived from the Wharton’s jelly of the umbilical cord to generate new skin more quickly.

These mesenchymal stem cells inside the Wharton’s jelly are uncommitted. Which means that when they are combined with agarose and fibrin (a blood clotting protein) skin and mucosal cells can be made. Doctors and researchers are very exiting to have found new uses for mesenchymal stem cells from Wharton’s jelly. Which have previously been unknown as an epithelial application for patients.

The conventional way of skin making is very time consuming and can not be delivered at the spot when needed. Artificial skins on the other hand are more quickly generated and can be stored so it is ready when it is needed. Thousands of skin grafts are performed each year for burn victims, for people with large wounds cosmetic surgery patients. Traditionally, this involves taking a large patch of skin (typically from the thigh) and removing the dermis and epidermis to transplant elsewhere on the body.

The artificial skin requires the use of Wharton’s jelly mesenchymal stem cells.

Once the epithelial tissues have been created, researchers can store it in tissue banks. If someone is brought into the hospital following a devastating burn or accident. The tissue is ready to graft immediately; not in a few weeks. The used skin stem cell are not fully differentiated when used, but after cell-cell junctions the stem cells will develop all of the necessary layers of normal epithelial tissue.

Mesenchymal Stem Cells from cord tissue

The mesenchymal stem cells are taken from the umbilical cord after the baby has been born. Which poses no risk to either the mother or the child. This method is relatively inexpensive and has been shown to be more efficient than stem cells derived from bone marrow.

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Heart attacks are the number one cause of death worldwide claiming more than 17 million lives each year. The effects of congestive heart failure present great challenges for scientist and doctors.

Stem cell biology represents a new medical frontier. Scientist are working toward to replace damaged heart cells and literally restore cardiac function using stem cells.

Stem cells have the ability to home into the damaged areas but also to initiate a cascade of biological events which both culminate in healing of the heart. For example, animal studies have demonstrated that stem cell therapy will cause new muscle cells to be formed through stimulation of dormant stem cells that are already inside the heart muscle.

Scientific Articles

Placental Mesenchymal and Cord Blood Stem Cell Therapy for Dilated Cardiomyopathy
Ichim T, Solano F, Brenes R, Glenn E, Chang J, Chan K, Riordan N.
– Reproductive BioMedicine Online 2008; 898-905

Combination of Stem Cell Therapy for Heart Failure
Ichim T, Solano F, Lara F, Paz Rodriguez J, Cristea O, Minev B, Ramos F, Woods E, Murphy M, Alexandrescu D, Patel A, Riordan N.– International Archives of Medicine 2010; 3:5

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Multiple sclerosis, known as MS, is a disease that can affect all nerves. It can cause problems with organs like eye, ear, muscles, and other basic body functions. The effects of the disease can be different for everyone. Which means that some have more severe symptoms than others.

MS is diagnosed when your immune system attacks the myelin (fatty material) of the nerve fiber. The fatty material is very important in signal transmission. Damage in signal transmission means your brain can’t send signals through your body correctly.

Cure for Multiple sclerosis

Researcher are looking for a cure for manny years now and a redical treatment seems to contain the answer.

The treatment seems very straightforward, wipes out the immune system and then regenerate again. This seems to halt progression of aggressive MS and even reverse its symptoms.

Scientists all around the globe are very exiting and data from clinical trials are showing interesting results.

But the radical treatment is at the same time very risky, and only likely to benefit a certain proportion of patients still in early stages of the disease.

The treatment is known as immunoablation and autologous hematopoietic stem cell transplantation. Doctors take stem cells from the patient bone marrow (hematopoietic stem cell are also found in large numbers in the umbilical cord) and bank them before giving a chemotherapy drugs that destroys the whole immune system.

The stem cells are then transplanted back into the body to generate a new disease free immune system without the problem of attacking nerve fibers.

13 years of data from clinical trial show zero patient relapsing and 70% experiencing a complete stop in disease progression.

In 40 percent of cases, patients saw lasting reversal of symptoms such as vision loss, muscle weakness and balance problems.

Some patients were able to return to school or work, get married and have children.

Risks of immunoablation and autologous hematopoietic stem cell transplantation.

The fact that patients have no immune system for a while makes them vulnerable for infectious. They also experience risks from the severe side effects of the chemo drugs used.

Survivor

“Thanks to this research I have been given a second chance at life.”,Jennifer Molson

Most promising medicine for relapsing multiple sclerosis

Immunoablation and autologous hematopoietic stem cell transplantation

Potential medicine for relapsing multiple sclerosis

Phase 3
Ocrelizumab
Cladribine
RPC1063
Laquinimod
Ponesimod
Ofatumumab

Phase 2
Anti-LINGO-1
ATX-MS-1467
Minocycline
Raltegravir
Amiselimod
Lipoic acid
Clemastine
ATL1102
Vatelizumab
Rituximab – development terminated

Potential treatments for primary progressive multiple sclerosis

Phase 3
Ocrelizumab
MD1003
Masitinib
Fingolimod

Phase 2
Fluoxetine
Ibudilast
Laquinimod
Natalizumab
Rituximab – development terminated

Potential treatments for secondary progressive multiple sclerosis

Phase 3
Siponimod
MD100
Masitinib

Phase 2
MS-SMART
Simvastatin
Riluzole
Amiloride
Fluoxetine
MIS416
Tcelna
Lipoic acid
Ibudilast
Anti-LINGO-1
Natalizumab
Rituximab – development terminated

Potential treatments for optic neuritis
Phenytoin
Anti-LINGO-1
Amiloride
MD1003

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Macular degeneration a well known disease that affects millions of people around the world. It is also the most common cause of vision loss. The disease causes deterioration of the retina on the spot known as the macula. The macula focuses vision and controls our ability to see things in fine detail. Since 2017 the disease is curable with stem cell therapy.

Patients with macular degeneration receive successful treatment with induced pluripotent stem cells. With stem cells differentiat in new retinal cells made in the laboratory, the therapy stops further degeneration. Induced pluripotent stem cells often created from regular adult cells. In this patient, the cells used to repair the damaged eye came from the patients own skin.

A team led by Masayo Takahashi, created induced pluripotent stem cells cells from a patient’s own skin cells. Then, they differentiated them to form cells to heal the retinal pigment epithelium. These cells help to support the retina, allowing the macular to interact with light, and restore visibility.

Successful treatment.

Once the cells are made they are patched together in a slither measuring 3 by 1 mm. The teams led by Masayo Takahashi aim to stop further degeneration. The treatments show that the procedure is technically successful: although the patients vision did not improve, the degeneration stopped.

The long term effect of induced pluripotent stem cells are unknown. Tissue formed with stem cells could cause mutations and mutations can cause cancer is one of the major concerns. In this specified cases the patients treated had no signs of cancer or any other complications.

In 2017 three people went blind after stem cell treatment, even though this treatment is completely different it shows that stem cell therapy must not be done by everyone and with every disease.

Because of the risks induced pluripotent stem cells are very controversial. More research is necessary on induced pluripotent stem cells and there is a need for other stem cells that can be used for treating Macular degeneration. An alternative and promising stem cells type are the mesenchymal stem cells found in high number in the umbilical cord.