PUBLIC RELEASE DATE:

23-Apr-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Apr. 23, 2014) People who have had a stroke, often suffer motor deficits with little potential to restore neurological function. However, a study conducted in Taiwan, that will be published in a future issue of Cell Transplantation, but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1168Chen, has found that when one group of stroke victims had their own peripheral blood stem cells (PBSCs) injected directly into the brain and a similar group did not, those who received the PBSCs experienced some "improvement in stroke scales and functional outcome." Those in the PBSC-injected group also received injections of the growth factor granulocyte-colony stimulating factor (G-CSF), known to be potentially neuroprotective.

"In this phase 2 study, we provide the first evidence that intracerebral injection of autologous (self-donated) PBSCs can improve motor function in those who have suffered a stroke and have motor deficits as a result," said study corresponding Dr. Woei-Cheng Shyu of the Center for Neuropsychiatry, Graduate Institute of Immunology and Translational Medicine Research Center, China Medical University in Taiwan. "Our study demonstrated that this therapeutic strategy was feasible and safe in stroke patients who suffered a prior stroke, but within five years from the onset of symptoms."

According to the authors, there has been little advance made in restoring neurological function following ischemic stroke. However, since neuronal death is the primary mechanism that limits functional recovery, stem cell therapy is emerging as a potentially effective regenerative approach. Once more PBSCs are being increasingly used as a self-donated source for cell therapies for regenerating skeletal muscle, heart and neurons. The PBSCs may need to be "amplified" with G-CSF, speculated the researchers.

All of the patients in the trial had suffered a stroke in the past, as long as five years prior to this study. At the end of a 12 month follow-up, the group of 15 patients with neurological deficits who received injections of PBSCs experienced neurological and functional improvement based on a number of clinical outcomes measures. The control group of 15 patients with neurological deficits that did not receive the PBSC injections did not experience the same beneficial outcomes.

The researchers reported that nine of the 15 patients undergoing PBSC transplantation experienced "positive motor evoked potentials" (MEPs) after transcranial magnetic stimulation, but why MEPs appeared in some of the transplanted group, but not all, was unclear.

"Despite this success, it should be noted that this was a preliminary study and, due to the small number of patients, are tentative," concluded the researchers. "In the future we plan to conduct a multi-center, large-scale, double blind, placebo-controlled randomized studies to better evaluate the effect of PBSC implantation in patients suffering from the effects of past stroke."

"This phase II study offers pilot clinical evidence supporting the use of autologous stem cell-based treatment for stroke" said Dr. Cesar V. Borlongan, Prof. of Neurosurgery and Director of the Center of Excellence for Aging & Brain Repair at the University of South Florida. "Clarification of the impact of G-CSF on the cells and whether other factors are necessary to maximize the benefit of cell transplantation, as well as further studies with a larger number of patients are necessary to determine equivocal safety and efficacy of this treatment".

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Autologous stem cell therapy improves motor function in chronic stroke victims

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Newswise A team of scientists led by a researcher from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has identified the cancer specific stem cell which causes gastric cancer. This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers.

The research group, led by Dr Chan Shing Leng, Research Assistant Professor at CSI Singapore, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer stem cells but not normal cells. Conceptualised by Dr Chan and Associate Professor Jimmy So, a Senior Consultant from the Department of Surgery at the National University Hospital Singapore, the study is also the first to be conducted with human gastric tissue specimens and took five years to complete. This novel study will be published in the research journal Cancer Research, the official journal of American Association of Cancer Research, in May 2014.

Gastric cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.

How CD44v8-10 serves as a biomarker

Many cancer cell types express high levels of a cell surface protein known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumour relapse. There are many forms of CD44 and the standard form of CD44, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem cells. This is critical as an ideal cancer target should mark only cancer cells but not normal cells.

Research by the team and other scientists in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analysed 53 patient tissue samples in conjunction with patient-derived xenograft models which are derived from intestinal type gastric cancer. The team is one of the few groups in the world to have a relatively large collection of patient-derived xenograft models for gastric cancer and the first to use these models for identification of gastric cancer stem cells. A total of eight cancer cell lines were used in this study, including six new cell lines which were established by the researchers.

The scientists discovered a cancer-specific CD44 variant, CD44v8-10 marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumour sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells. As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available and doctors rely on endoscopy for the screening and diagnosis of this disease.

Said Dr Chan, With our findings, we can now work on developing drugs that would recognise and attack the cancer stem cells only, reducing the side effects on normal cells. With additional funding, we aim to have a drug that can show efficacy in our models within three years.

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Scientists Identify Cancer Specific Cell for Potential Targeted Treatment of Gastric Cancer