Developing Sperm Used in the Creation of Stem Cells

Scientists at Johns Hopkins University School of Medicine have realized that the discovery of how to revert adult cells into their elemental stem cell state might hold the key to what exactly stem cell therapy can accomplish. Through their research, these scientists have been able to discover those key molecular players that have mainly been accountable for the fruit fly sperm cells reversion process. In an online report that was published in Cell Stem Cell, it was noted that two very important proteins- Jak and STAT- had been responsible for redirecting sperm becoming cells into stem cells. An associate professor of cell biology at the Johns Hopkins University School of Medicine, Dr. Erika Matunis stated that earlier research conducted by the group showed that it was possible to convert sperm into stem cell, although the way to do so still remained a mystery. “Dedifferentiation is an extremely motivating and appealing wonder that has had its occurrence in a variety of stem cell populations and as such, we wanted to know everything that we could about the process,” says Dr. Matunis.

Similar to stem cells, the fly testis also contained nine stem cells that were divided to create daughter cells. Out of these two, one was differentiated into an adult cell or a sperm cell while the other remained a stem cell. The research team at Johns Hopkins University School of Medicine genetically altered the flies in order to find out the reason behind the dedifferentiation of these sperm cells. The flies were altered so that both the cells would transform into sperm resulting in the stem cell population of the testes becoming nothing. A week after the genetic modification, it was found that the two stem cells had repopulated from the fly testes.

It had long been suspected that two proteins, Jak and STAT were not only known to work together in helping stem cells, but were also responsible for dedifferentiation. “By genetically altering the flies, we were able to reduce the amount of activity in the STAT and Jak proteins. We now know that it is possible to interfere with the process of dedifferentiation by interfering with these two proteins in the fly testis.

The team realized that fewer cells would revert back to stem cells if there was interference with the two proteins. By counting the number of cells it was found that unlike normal Jak-STAT activity where 97% of the testes regained stem cells, such interference caused merely 60% of the testes to regain stem cells.

Human Stem Cells Used to Manufacture Red Blood Cells that can Glow

 Scientists at the Monash University in Victoria have managed to modify human embryonic stem cells so that they can ‘glow’ when transformed into red blood cells. These customized embryonic cells are representations of the first focal step taken towards the generation of completely functional red blood cells. Although human embryonic stem cells have the capability of being modified to fit any required cell within the body, it still remains a challenge to try and turn these embryonic cells in any specific helpful cells. For this reason, the findings at Monash have represented a major breakthrough in scientific study.

Studies are now being conducted on such human embryonic stem cells so as to try and find an answer to a variety of complex questions regarding human development. One of the primary objectives in the study of such stem cells is to find out how they can become differentiated cells forming part of the organs and tissues of the body. Many diseases such as cancer as well as birth defects have been attributed to the abnormal separation of such embryonic cells. To completely understand the controls of such cells, human embryonic stem cell research is currently being carried on.

Led by Professor Ed Stanley and Professor Andrew Elefanty as well as other leading scientists from the Murdoch Children’s Research Institute, the findings of the research which were funded by the Australian Stem Cell Center (ASCC) were published in the journal, ‘Nature Methods’. The ASCC helps to track the demarcation and transfiguration of the embryonic stem cells into red blood cells.

The ASCC’s Scientific Director, Professor Joe Sambrook was quoted as saying, “The fantastic work ethics of the Elefanty-Stanley team has finally paid dividends and has brought to light the differentiation pathway which has finally led to our better understanding of the manifestation of adult hemoglobin genes.”

For quite some time, it had remained a scientific challenge to be able to turn human embryonic cells into other types of cells. Through their research, the team managed to incandesce red into the ErythRED embryonic stem cells when mixed with hemoglobin. This brings hope to the fact that in future, researchers would be able to enhance the conditions that bring about the thriving of such cells. This ErythRED cell line can lead to the improved creation of red blood cells and can also be used as a means for monitoring any transplanted animal model cells.

The research was supported by the Juvenile Diabetes Research Foundation, the National Health and Medical Research Foundation and the Australian Stem Cell Centre.

Stopping cancer stem cells through lung cancer Oncogene

At the Mayo Clinic in Florida, scientists have unearthed that  PKCiota – a lung cancer oncogene- has been responsible for the proliferation of lung cancer stem cells. These powerful and very rare stem cells are responsible for the manufacture other cells that lead to the building up of various tumors. These cancer causing stem cells are also very resistant to chemotherapy.

PKCiota is a human oncogene, in other words, it is an abnormal gene that is used by various malignant cancers to grow and survive. Most lung cancers are able to genetically alter as well as over-express this PKCiota which in turn results in the patient becoming very weak and having a very low rate of survival.

In an issue of Cancer Research, a study showed that it was capable of stopping the growth of any cancerous stem cells through the use of a particular agent called aurothiomalate. This aurothiomalate is currently being tested at the Mayo Clinic and is in a clinical trial of phase I.

Alan Fields, chair of the Department of Cancer Biology at Mayo Clinic and professor of pharmacology in the College of medicine, who is also the senior analyst in the study said, “Our research has proved that PKCiota is needed at the earliest stages and aids in the growth tumor initiating cancerous stem cells which ultimately leads to lung cancer.”

“Most common lung cancers are caused by these lung cancer stem cells and so, it is vital that such cancerous stem cells be disrupted in order for any therapeutic treatment to work. Our impending research has shown that aurothiomalate can in fact be used to effectively target such stem cells.”

Used once upon a time to treat rheumatoid arthritis, aurothiomalate has now also been proved to be very effective in targeting PKCiota. There is a trial phase I that is currently being conducted on various patients at the Mayo Clinic in Arizona and Minnesota and depending upon the results in phase I, phase II has been scheduled to combine aurothiomalate with various other agents that are capable of slowing down the growth of such cancerous cells.

Although, it was previously known that PKCiota was able to maintain tumor growth, these new findings show that PKCiota is also responsible for the initial development of lung cancer. Scientist for long have known that cancer stem cells were capable of initially bringing about tumors, however, the discovery of aurothiomalate has now proved that these stem cells are not as resistant to tumors as previously thought.

Human cell transplantation is able to prolong survival of mice

A recently conducted study has shown that the successful transplantation of human neural stem cells has been able to provide substantial improvement in a rare hereditary neurodegenerative disease. These findings which were published in the September issue of Cell Stem Cell show that a critical enzyme which was missing from the brains of the experimented mice was provided for by the transplanted cells. This study has proved that there might be hope for those patients that are currently suffering from any types of devastating or untreatable diseases.

One type of neurodegenerative disease that is found in children is the Infantile Neuronal Ceroif Lipofuscinosis (INCL). Also known as Batten disease, INCL is formed by a deficiency of the enzyme palmitoyl protein thioesterase-1 (PPT-1) that is created by a particular gene. A deficiency of PPT1 results in an accumulation of a cellular lipid known as lipofuscin. Any accumulation of this lipofuscin can lead to visual impairment, reduced motor and cognitive skills, neuron death, seizures and also cause premature death.

Currently, it is almost impossible to get PPT1 enzymes in the brain and so intravenous enzyme treatment is not an apt solution. However, it has been conjectured that donor cells that have been transplanted would be capable of supplying the needed enzymes directly into the brain. A mouse model that is capable of exactly replicating many aspects of human disease has been created and is now being used to find whether such stem cell replacement would be beneficial or not. Led by Dr. Nobuko Uchida, a study was carried out to test this hypothesis. “We made use of nontumorigenic, normal and nongenetically modified human cells to ably deliver the enzymes into the modeled mice. We transmitted these neural stem cells as they are self renewing and provide a permanent production of any missing enzymes.” The transplanted human neural stem cells were capable of matching and delivering the required enzymes to the modeled mice, while at the same time also providing a production of PPT1 to bring about significant improvement. After the replacement therapy, the INCL infected mice showed signs of reduced loss of motor coordination, less lipofuscin and greater neuroprotection.

These findings have shown that the direct transplant of such stem cells into the brains of those that suffer from INCL might be able to provide a long lasting and continuous supply of the missing PPT1 as well as some therapeutic benefits, thereby providing a potential medical breakthrough in combating such a disease.

Gene therapy not the cause of arthritis patient death

Medpage Today published on July 08, 2009 reported a 32 year old women death who participated in the gene trial therapy for rheumatic arthritis. The patient died after 22 days of treatment. This incident has put a halt to all the clinical tests that was going on related to gene therapy. Actually the researchers were testing a drug named experimentally as tgACC94. This drug is based on the recombinant adeno-associated virus (AAV) derived vector. It carries the tumor necrosis factor receptor (TNF-receptor) gene to block the inflammation.

After investigation the researchers say that the death of the patient is not because of the gene therapy treatment for rheumatic arthritis. It is because of the wide spread histoplasmosis. Histoplasmosis is a normal fungal infection but in this case it has gone deadly as the result of immunosuppressant therapy. The patient was under immunosuppressant therapy for few years she was under the medication of adaimumab, methotrexate and prednisone. These drugs have only increased the risk of histoplasma fungus, said the researchers. They also add that the combination of histoplasmosis and retroperitoneal hematoma has only led to patients death. It is a well known thing that the risk is more when a patient affected by histoplasmosis takes TNF antagonists. The important explanation the researchers say is that she was already infected by the histoplasmosis fungus when she was receiving her second dosage of tgAAC94 as a part of her gene therapy. After the second dosage she was suffering with large number of symptoms like fever, vomiting, abdominal pain etc. The symptoms started getting worse day by day and she was hospitalized. Finally she was suffering from large abdominal hematoma, liver damage and kidney failure. After three weeks of suffering from all these symptoms from the day the second dosage for gene therapy was given she died on 24^th July. Some people say, the death can be avoided if the researchers had taken enough care of the patient at the beginning itself when she started showing some negative symptoms. If she would have brought under complete monitoring at that time itself definitely her death would have been avoided.

Elizabeth L.Hohman, MD, of partners human research committee in Boston, wrote in an editorial that this incident has taught a number of lessons to the researchers, mainly making them to concentrate about the endemic infections in the area where the patients are residing. This incident has cautioned all the researchers around the globe. This has made them to take a keen note of all the endemic diseases that are in the prevailing in patient areas who all are receiving TNF antagonist drugs. And also in addition to that the researchers have come to know about the importance of a proper complete monitoring system of the patients who fall ill when they are under such researchers. Because of this negative result in gene therapy people will come to a thought that acceptance of a gene therapy approach for non genetic diseases such as arthritis is marginal and the serious adverse effect of the treatment could even destroy the entire activity.