It has long been known that "Lewy bodies", one of the hallmarks of Parkinson’s disease and related types of neurodegenerative conditions, are formed from the aggregate accumulation of the synaptic protein alpha-synuclein. It has also been understood that the progression of such diseases is associated with the spreading of the Lewy bodies, which continue to infiltrate more and more regions of the brain. It has not previously been understood, however, exactly how the Lewy bodies are able to spread. Now, researchers are one step closer to a full elucidation of the underlying cellular and molecular mechanisms by which Lewy bodies ultimately invade the entire brain.

At the crux of the phenomenon is the neuron-to-neuron transmission of the alpha-synuclein itself – a new discovery made by collaborating scientists at the UC-San Diego School of Medicine and Konkuk University in Seoul, South Korea. According to Dr. Paula Desplats, lead author of the study and project scientist in the UC-San Diego Department of Neurosciences, "This discovery of cell-to-cell transmission of this protein may explain how alpha-synuclein aggregates can pass to new, healthy cells. We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures."

The discovery is believed to have important implications for the use of stem cell therapies in the treatment of Parkinson’s disease and other "proteinopathies", since stem cells that are transplanted into the brains of patients are also vulnerable to eventual degeneration if a number of conditions are not suitable. As Dr. Eliezer Masliah, professor of neurosciences and pathology at the UC-San Diego School of Medicine, explains, "Our findings indicate that the stem cells used to replace lost or damaged cells in the brains of Parkinson’s disease patients are also susceptible to degeneration. Knowledge of the molecular basis of the intercellular transmission of alpha-synuclein may result in improved stem-cell-based therapies with long lasting benefits, by preventing the grafted cells to uptake alpha-synuclein or by making them more efficient in clearing the accumulated alpha-synuclein."

In most though not all Parkinson’s patients, the progression of alpha-synuclein is observable in a predictable pattern which begins in the lower brainstem and spreads first to the limbic system before ultimately attacking higher level cognitive functions in the neocortex. Prior to this study, previous findings had indicated that alpha-synuclein also spreads to transplanted neurons in Parkinson’s patients, an observation which led to a hypothesis of disease progression via neuron-to-neuron transmission. In the current study, which was specifically designed to test that hypothesis, the scientists discovered that the alpha-synuclein is transmitted between neurons via a process known as endocytosis, in which cells are able to absorb proteins from the extracellular media through their cell membranes. In addition to demonstrating that the accumulation of alpha-synuclein can be diminished by blocking the endocytic pathway, the scientists also found that inhibited lysosomal activity accelerates the accumulation of alpha-synuclein, since normal lysosomes would ordinarily help remove the accumulated aggregates. The scientists then demonstrated in a transgenic animal model how the alpha-synuclein is transmitted directly from host to grafted cells. Despite the fact that the laboratory animals had received fresh, healthy stem cells, within four weeks of the transplantation their brains had been overrun with Lewy bodies. Such findings would explain why human Parkinson’s patients who had received neuronal transplants usually succumb to the disease anyway, since the Lewy bodies that characterize Parkinson’s are still able to ravage the newly transplanted neurons.

As a result of these findings, researchers are now turning their attention to the strategic development of mechanisms by which stem cell therapy may be administered to Parkinson’s patients in conjunction with the blocking of endocytic pathways, and also in conjunction with the enhancement of normal lysosomal activity.

Today three universities in Nebraska have announced that they are to receive state grants in order to conduct stem cell research that strictly and exclusively involves adult stem cells, not embryonic stem cells. The recipients include Creighton University School of Medicine, the University of Nebraska Medical Center (UNMC), and the University of Nebraska at Lincoln, each of whom have been awarded a $150,000 research grant.

The three grants have been awarded in accordance with the Nebraska Stem Cell Research Act of 2008, which stipulates that neither state money nor state facilities may be used for research purposes in which the destruction of a human embryo is involved. Nonembryonic, adult stem cell research is strongly encouraged under the Act, and funding for the grants comes from the state’s tobacco lawsuit settlement funds.

The grants were recommended by Nebraska’s Stem Cell Advisory Committee, which consists of deans of the medical schools at Creighton and UNMC as well as four scientists from outside of Nebraska.

According to Tom Murray, dean of research at Creighton University School of Medicine, the grant is also in accordance with Creighton’s policy against the destruction of human embryos. Researchers at Creighton plan to use the grant money to conduct research on stem cells in mice for the development of therapeutic strategies in the treatment of hearing loss. Researchers at UNMC intend to use the grant money to study human adult stem cells in the treatment of vision loss.

A patient with multiple myeloma has been treated with his own autologous adult stem cells, and is now cancer-free.

Since receiving a kidney transplant 15 years ago, the patient – who has chosen to remain anonymous – has had to take immuno-suppressant drugs. Upon being diagnosed with multiple myeloma a year and a half ago, the patient suddenly faced a dilemma: reduction of the immunosuppressing drugs might have allowed his body to fight the cancer, but also could have resulted in rejection of the transplanted kidney. His doctors therefore recommended that he undergo treatment with his own bone-marrow-derived autologous adult stem cells.

The procedure was performed a month ago on the 49-year-old patient. Now, a PET (positron emission tomography) scan revealed that he is free of cancer.

According to nephrologist Dr. Madan Bahadur, this patient "is the first kidney transplant patient in the world to undergo a stem cell transplant to beat multiple myeloma after ablative chemotherapy." In addition to Dr. Bahadur, the patient was also treated by hematologist Dr. Sameer Shah and oncologist Dr. Ganpati Bhat at Mumbai’s Jaslok Hospital.

According to Dr. V. Hase, chief of nephrology at Mumbai’s King Edward Memorial Hospital, "The Jaslok patient’s case is of great academic interest. Firstly, it is rare for a kidney transplant patient to develop multiple myeloma. Secondly, no transplant patient in India has undergone a stem cell transplant as a rescue mission against cancer."

As Dr. Hase further adds, in light of the fact that renal failure is a known complication of multiple myeloma, "In the Western world, multiple myeloma patients would undergo the stem cell transplant first and a renal transplant later. But in the Mumbai case, the opposite has happened."

The results of the transplant are scheduled to appear in the European journal, Nephrology Dialysis Transplant.

Two researchers at the University of Piitsburgh have won a patent dispute in the Federal Circuit over a laboratory procedure by which adult stem cells derived from human adipose (fat) tissue may be differentiated into cartilage, muscle and bone cells. The Court rejected a bid by researchers at UCLA who had claimed credit as co-inventors of the process.

University of Pittsburgh researchers Drs. Adam Katz and Ramon Llull first began researching adipose-derived adult stem cells in the 1990s. Along with Dr. Marc Hedrick, who temporarily joined their laboratory at a later date, the researchers formally announced in April of 1998 that the adipose-derived stem cells could be differentiated into cartilage, muscle and bone tissue. The actual date of the discovery, however, was listed as October of 1996.

At the crux of the dispute is the fact that Dr. Hedrick temporarily joined the University of Pittsburgh laboratory under a year-long fellowship, at the completion of which he returned to UCLA where he continued to study adult stem cells of adipose origin along with his UCLA colleagues Drs. Hermann Peter Lorenz, Min Zhu, and Propser Benhaim.

Both teams of researchers at both universities then filed separate patent applications for the same laboratory methods and materials by which the stem cells are differentiated into other tissue types. Although the University of Pittsburgh had originally filed an international patent application in 2000 on which Katz, Llull, Hedrick, Lorenz, Zhu and Benhaim were all listed as co-inventors, Katz and Llull later sought to remove the names of Hedrick and the other UCLA researchers from the application.

When the UCLA researchers challenged the claim by Katz and Llull as sole inventors of the process, the district court of Pittsburgh ruled in favor of Katz and Llull, decreeing that these two researchers had invented the procedure prior to Hedrick’s fellowship. The UCLA team of researchers then appealed the decision, claiming that the research was "inconclusive" until Hedrick had been added to the team – a claim which was overruled in Washington, D.C. by the U.S. Federal Court of Appeals.

According to the presiding judge, the Honorable H. Robert Mayer, who has served as Chief Circuit Judge of the United States Court of Appeals for the Federal Circuit since his appointment as such in 2004, "Proof that the invention works to a scientific certainty is reduction to practice. Therefore, because the district court found evidence that Katz and Llull formed a definite and permanent idea of the cells’ inventive qualities, and had in fact observed them, it is immaterial that their knowledge was not scientifically certain and that the [defendant] researchers helped them gain such scientific certainty."

Law suits are not uncommon in the biotech industry, and challenges to patent and copyright law are occurring with increasing frequency every day, especially in the stem cell field. No doubt this recent ruling – in favor of the initiating scientists who had "formed a definite and permanent idea" of the outcome despite the fact that such impressions were "not scientifically certain" – will now be cited as a precedent in future legal disputes of a similar nature.

Researchers at the Imperial College in London have made some important discoveries in the process by which different types of stem cells differentiate into bone. The findings have direct applications to the development of stem cell therapies for the treatment of various bone injuries.

Specifically, the scientists found significant differences in "bone-like" material that was grown from 3 different types of cells taken from mice. Two of those cell types – namely, osteoblasts that were derived from the skulls of the mice, and mesenchymal stem cells that were derived from the bone marrow of the mice – were found to be capable of differentiating into a tissue that resembles "native" bone in all of its features, including matrix complexity and mechanical stiffness. The third type, however, was less promising. When the scientists tried to differentiate mouse embryonic stem cells into bone, the result was a tissue that was much less stiff and not as complex as real bone in its mineral composition. Upon further analysis with high resolution electron microscopy, a nano-indenter, and laser-based Raman spectroscopy, the scientists found that only the bone tissue that was differentiated from the two types of adult stem cells actually possessed both the microscopic and the macroscopic properties of real bone.

According to Dr. Molly Stevens of the Department of Materials and the Institute of Biomedical Engineering at the Imperial College of London, "Many patients who have had bone removed because of tumors or accidents live in real pain. By repairing bone defect sites in the body with bone-like material that best mimics the properties of their real bone, we could improve their lives immeasurably. Our study provides an important insight into how different cell sources can really influence the quality of bone that we can produce. It brings us one step closer to developing materials that will have the highest chance of success when implanted into patients."

A number of researchers around the world are currently working on the task of growing small "nodules" of new bone from stem cells in the laboratory, and a number of clinical trials are already underway. Now, the results of this new study allow scientists to pinpoint more precisely which type of stem cell is the best type to be the originating source of the bone.

Researchers at the University of Adelaide have been using adult stem cells to treat gum disease in preclinical animal trials, with significant success. Now, the scientists have been awarded $200,000 in funding from the Australian Stem Cell Centre to expand their research to humans.

According to Dr. Mark Bartold of the University of Adelaide, "We’ve got the proof, in principle, and can regrow a lot of bone around the teeth and restore some of the damage that has been done. As with any new technology, we’ve still got a little way to go. There’s a lot of unanswered questions and more will pop up along the way."

In the past, Dr. Bartold and his colleagues have taken adult stem cells from the jawbones of sheep and pigs, which were then cultured and re-implanted into other animals in whom gum disease had caused bone loss around their teeth. Specifically, the adult stem cells were derived from the ligament that secures the teeth into the jawbones of the animals. Now, the method will be applied to people.

According to Dr. Bartold, it has been estimated that approximately 60% of all Australians suffer from some form of gum disease, in whom it is not uncommon to see advanced stages of periodontitis. In theory, therefore, a cell-based therapy for gum diseases would have a large market in Australia.