People who have RA overproduce a protein called tumor necrosis factor (TNF), which causes the inflammation and damage to the bones, cartilage and tissue. Anti-TNF drugs can block the action of the protein and reduce inflammation. Etanercept® (marketed under the trade name Enbrel) is a type of anti-TNF drug called a biologic that for years has been prescribed to treat RA. However, it can’t be targeted specifically to the site of the arthritis and, thus, requires higher doses that can cause serious side effects including fatal infections, multiple sclerosis, seizures, heart failure, cancer and more.
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“As a result, there has been significant interest in developing RPE culture systems both to study AMD disease mechanisms and to provide substrate for possible cell-based therapies. Because of their indefinite self-renewal, human pluripotent stem cells (hPSCs) have the potential to provide an unlimited supply of RPE-like cells,” noted Donald Zack, M.D., Ph.D., who with Julien Maruotti, Ph.D., led the team of researchers from the Wilmer Institute, Johns Hopkins University School of Medicine in Baltimore, Md., and the Institute of Vision in Paris in conducting the study.
“However, most of the currently accepted methods in use for deriving RPE cells from hPSC involve time-and-labor-consuming steps done by hand, and they don’t yield large enough amount of the differentiated cells – which has posed a problem when trying to use them to develop potential new therapies,” Dr. Maruotti added.
ALS (commonly known as Lou Gehrig’s disease) is characterized by the degeneration and death of the body’s motor neurons, leading to muscle atrophy, paralysis and death due to failure of the respiratory muscles. Despite studies that have improved our understanding of how ALS develops, there are no effective treatments. However, stem cell based-therapies have emerged as a potential solution.
“The transplantation of stem-cell derived neural progenitors may have beneficial effect not only for the replacement of motor neurons already lost, but also in counteracting degeneration and death of motor neurons,” said Roland Pochet, Ph.D., of the Université libre de Bruxelles, Belgium. He headed up the research team that included scientists from INSERM et Université Paris-Sud, and the Pasteur Institute, also in Paris, and Hannover Medical School in Germany.
“NK cells show promise for cancer therapy,” said Dan Kaufman, M.D., Ph.D., of the Stem Cell Institute, University of Minnesota in Minneapolis. “They are part of the innate immune system and exhibit potent antitumor activity without the need for donor matching and prior treatment.
“Moreover, the derivation of NK cells from pluripotent stem cells could provide an unlimited source of lymphocytes for ‘off-the-shelf’ therapy.”
Dr. Kaufman was the lead investigator on the study that included colleagues from UM as well as from the Integrated Center of Cellular Therapy and Regenerative Medicine, St. Anne's University Hospital Brno, Brno, Czech Republic; and the University of Texas, Houston.
Interestingly, the regenerated bone is also hard, rather than the spongy kind normally found in the jaw.
The new study is a follow-up to previous investigations by an international team of researchers in which they discovered that mesenchymal stem cells taken from dental pulp and seeded on a collagen scaffold successfully repaired the mandible bone. In this latest work, they checked on patients who had received the mandible bone grafts three years earlier to assess the stability and quality of the regenerated bone and vessel network.
They found the new bone had normal function and was richly vascularized, although was much more compact than the spongy type normally found in the mandible. The team theorized that, most probably, regeneration of compact bone occurs because grafted dental-pulp stem cells do not follow the local signals of the surrounding spongy bone.
Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s Disease, is a rapidly deteriorating neurological condition affecting five out of every 100,000 people worldwide, mainly after the age of 50. The average survival time is only three years.
While no effective treatment exists, preliminary studies suggest that the quality of life and even life expectancy itself could be improved in patients who receive stem cell infusions. However, questions remain about the capacity of these cells to “take hold” and turn into neurons.
Kidney transplants have long been the treatment of choice for many patients with end-stage renal disease, and the short-term results are excellent. But unfortunately, the viability of these kidneys over time has not improved accordingly, often due to fibrosis, which is a scarring of the transplanted organ generally caused by the immune system rejecting it.
The LUMC team, led by Marlies E.J. Reinders, M.D, Ph.D., and Ton J. Rabelink, M.D., Ph.D., decided to test whether stem cells might keep fibrosis in check. They focused on mesenchymal stromal cells, a type of stem cell found throughout the body, including in bone marrow.
“Mesenchymal stromal cells (MSCs) are an interesting candidate due to their immunosuppressive and regenerative properties,” Dr. Reinders explained. “Of importance, no clinical studies have investigated their effects on rejection and fibrosis in organ transplantation.”
In DMD, the most common form of muscular dystrophy, patients lack a large, rod-like protein called dystrophin located primarily in muscles used for movement and in heart muscle. The dystrophin is part of a group of proteins that acts as an anchor, connecting each muscle cell's structural framework with the lattice of proteins and other molecules outside the cell. Without dystrophin, many of the muscle cells in the heart are damaged, subsequently die and are replaced by connective tissue.
“Many Duchenne MD patients suffer from dilated cardiomyopathy (DCM), a condition in which the chambers of the heart are enlarged and weakened,” explained the study’s lead author, Suzanne Berry, Ph.D. “As a result the heart can’t efficiently pump blood to the body and many patients eventually die. We hypothesized that mesoangioblast stem cells (ADM) found in the walls of large blood vessels, in this case the aorta, would restore dystrophin and therefore alleviate or prevent DCM.”
Scientists Daniel Peterson and Laura Shin used MSC cells extracted from human bone marrow and grafted them into wounds of healthy mice and mice with diabetes. Mice in both groups each had two separate wounds to better allow the researchers to study the precise role the cells played in healing.
Some mice in each group received MSC cells in one wound while others did not receive the cells at all.
After studying the differences in healing, signaling and cell populations in the mice, Peterson and Shin learned that both normal and impaired mice given MSC cells healed more quickly, even in wounds that did not receive direct MSC cell grafts.
“The mice that received MSC cells demonstrated a systemic response,” Peterson said. “This suggests that the key to repairing injured tissue does not hinge on where you place the MSC cells in the body, but on learning exactly how the MSC cells recruit their counterparts already in the body.”
The study, funded by the British Heart Foundation (BHF), Medical Research Council (MRC) and Wellcome Trust, outlines a way for scientists to get the cells they need to make induced pluripotent stem (iPS) cells (3) from a routine blood sample. Previously scientists have struggled to find an appropriate type of cell in the blood that can be turned into a stem cell, and often make iPS cells from skin or other tissues, which can require a surgical procedure, like a biopsy.
Dr Amer Rana and his colleagues at the University of Cambridge grew patients’ blood in the lab and isolated what are known as ‘late outgrowth endothelial progenitor cells’ (L-EPCs) to turn into iPS cells. The iPS cells can then be turned into any other cell in the body, including blood vessel cells or heart cells – using different cocktails of chemicals. Scientists use these cells to study disease, and ultimately hope to grow them into tissue to repair the damage caused by heart and circulatory diseases.