Putnam Valley, NY. (March 2, 2016) - Studies scheduled to be published in the April, 2016 issue of Cell Transplantation (issue 25(4)) were presented in 2015 at the 22nd Annual Meeting of the American Society for Neural Therapy and Repair (ASNTR), a society for scientists whose research is focused on understanding the causes of various neurological injuries and diseases and developing potential therapies such as cell therapy, gene therapy, and pharmacological interventions.
Among the presentations were studies using cell therapies to address peripheral neuropathic pain, motor function deficits following stroke, and the neurological symptoms of both Alzheimer's disease and Huntington's disease.
MSCs for treating neuropathology in Alzheimer's disease
Current treatments for Alzheimer's disease (AD) are only moderately effective and target only a few symptoms or pathways associated with AD. Now, researchers are testing adult mesenchymal cells (MSCs) to see if they offer potential AD treatments.
"MSCs offer an excellent source of stem cells for transplantation in AD patients," explained study co-author Dr. Gary Dunbar of Central Michigan University, and the outgoing 2015 ASNTR president. "They are multipotent cells, which means that they are able to differentiate into many different cell types such as blood, bone, muscle, fat and neural cells."
The goal of their study was to transplant MSCs into brain regions of mice modeled with AD and compare the behavioral and pathological effects to those of AD mice not transplanted with cells. They found that the transplanted MSCs reduced learning deficits in the mice, especially when the cells were transplanted into the lateral ventricles as opposed to the hippocampus.
This study, scheduled to be published in the 25(4) special ASNTR issue of Cell Transplantation, is freely available on-line as an unedited, early epub, at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1529_Matchynski-Franks_et_al
Contact: Dr. Gary L. Dubar, Health Professional Bldg, HP 2182, Central Michigan University, 1280 E Campus Dr., Mt. Pleasant, MI 48859
Email: Gary.dunbar@cmich.edu
Ph: (989) 774 3282
Fax: (989) 774-2552
Citation: Matchynski-Franks, J. J.; Pappas, C.; Rossignol, J.; Reinke, T.; Fink, K.; Crane, A.; Twite, A.; Lowrance, S. A.; Song, C.; Dunbar, G. L. Mesenchymal stem cells as treatment for behavioral deficits and neuropathology in the 5xFAD mouse model of Alzheimer's disease. Appeared or available online: February 2, 2016.
Recombinant GABAergic cells and peripheral neuropathic pain
The underlying mechanism of chronic neuropathic pain involves changes in several pain signaling pathways. Knowing this, researchers have focused on cell therapies and gene manipulation to affect events in the spinal cord where signaling takes place. As a proof-of-concept study for the management of chronic pain through intraspinal transplantation following injury to peripheral nerves, in this study the researchers employed recombinant (genetically engineered) cell therapy using GABAeric cells. They evaluated the therapeutic effect of GABAeric cells that produce the pain-reducing peptide Serine1-histogranin (SHG). They found that test animals experienced a reduction in sensitivity to heat and mechanical stimuli when compared to controls that did not receive the cell therapy.
This study is scheduled to be published in the 25(4) special ASNTR issue of Cell Transplantation, and is freely available on-line as an unedited, early epub, at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1522_Jergova_et_al
Contact: Dr. Stanislava Jergova, Miller School of Medicine, Miami Project, University of Miami, Miami, FL 1095 NW 14th Terrace, Miami, FL 33136 USA
Email: sjergova@miami.edu
Ph: +(305) 243 6038
Fax: (305) 243-3923
Citation: Jergova, S.; Gajavelli, S.; Varghese, M. S.; Shekane, P.; Sagen, J. Analgesic effect of recombinant GABAergic cells in a model of peripheral neuropathic pain. Appeared or available online: January 26, 2016.
Huntington's disease and mutant alleles
Huntington's disease (HD) is a debilitating, inherited neurodegenerative disease for which there is no cure. Symptoms of HD include cognitive impairment affecting memory and reasoning and personality changes, manifested as depression and anxiety. HD is caused by abnormal gene repetitions and the only therapies available are palliative therapies aimed at symptom reduction.
However, using mouse models of HD, scientists have begun to uncover the effects of the mutant huntingtin gene and make attempts at repressing the gene associated with the disease. Researchers are targeting gene abnormalities using "transcription activator-like effectors" (TALE) to target gene variations (single-nucleotide polymorphisms, or SNPs, in mutant genes, 190 of which have been associated with the mutant gene (huntingtin). "We targeted the mutant huntingtin gene with TALES to affect unique DNA sequences," said Dr. Kyle Fink of the University of California Davis' Institute for Regenerative Cures. "The targeting approaches have the potential to become potent therapies that can be adapted to a wide range of gene repeat disorders and other disease for which there is a known gene mutation."
This study is scheduled to be published in the 25(4) special ASNTR issue of Cell Transplantation, and is freely available on-line as an unedited, early epub, at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1537_Fink_et_al
Contact: Dr. Kyle Fink, Institute for regenerative Cures, Rm 1300, 2921 Stockton Blvd., Sacramento, CA 95817
Email: kdfink@ucdavis.edu
Ph: (916) 703-9300
Fax: (916) 703-9310
Citation: Fink, K. D.; Deng, P.; Gutierrez, J.; Anderson, J. S.; Torrest, A.; Komarla, A.; Kalomoiris, S.; Cary, W.; Anderson, J. D.; Gruenloh, W.; Duffy, A.; Tempkin, T.; Wheelock, V.; Segal, D. J.; Nolta, J. A. Allele-specific reduction of the mutant huntingtin allele using transcription activator-like effectors in human Huntington's disease fibroblasts. Appeared or available on-line at: February 4, 2016.
Human ganglionic eminence grafts improve motor function in rat model of Huntington's disease
In this study, brain tissue from human and rat whole ganglionic eminence (hWGE and rWGE, respectively) were grafted into rat models of HD. The results demonstrated that the clinically applicable hWGE grafts and the rWGE grafts were comparable in their ability to improve motor deficits in HD rats. The researchers suggested that fundamental differences between human and rodent brain development may account for some of the observed differences in how the WGE grafts matured and integrated into the host. The researchers concluded that further studies are needed to determine optimal timing for transplantation and the effect of these grafts on cognitive functions of HD animals.
This study is scheduled to be published in the 25(4) special ASNTR issue of Cell Transplantation, and is freely available on-line as an unedited, early epub, at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1513_Lelos_et_al
Contact: Dr. Mariah J. Lelos, School of Biosciences, Cardiff University, Museum Avenue Cardiff CF10 3AX,
Wales, UK
Email: lelosmj@cf.ac.uk
Fax: + 44 (0)2920 876749
Ph: + 44 (0)2920 874112
Citation: Lelos, M. J.; Roberton, V. H.; Harrison, C.; Eriksen, P.; Torres, E. M.; Clinch, S. P.; Rosser, A. E.; Dunnett, S. B. Direct Comparison of Rat- and Human-Derived Ganglionic Eminence Tissue Grafts on Motor Function. Cell Transplant. Appeared or available on-line: December 29, 2015.
Combination of growth factors improves motor function and brain pathology following stroke
Stroke is a brain injury caused by ischemia, a blockage of blood vessels that can result in neurological and motor deficits and long-term disability. Since stroke predominantly affects the elderly, this study focused on the effects of hematopoietic (blood-derived) growth factors on ischemic stroke in aged mice. Two growth factors - stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) - were administered to mice daily for different periods of time (one week and two weeks) after a stroke was induced. While treatment for two weeks did not appear to be more effective than one week of treatment, there was decreased fibrinogen (a component in plasma that is linked with stroke) in both groups and motor function seemed to improve as well. Results from the study suggested that factors derived from stem cells may be able to exert therapeutic effects similar to those offered by the cells themselves.
This study is scheduled to be published in the 25(4) special ASNTR issue of Cell Transplantation, and is freely available on-line as an unedited, early epub, at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1544_Liu_et_al
Contact: Dr. Li-Ru Zhao, Department of Neurosurgery, State University of New York Upstate Medical University, 750 E. Adams St., Syracuse, NY 13210
Email: ZHAOL@upstate.edu
Fax: + 1 315 464 5504
Ph: + 1 315 464 8470
Citation: Liu, Y.; Popescu, M.; Longo, S.; Gao, M.; Wang, D.; McGillis, S.; Zhao, L-R. Fibrinogen reduction and motor function improvement by hematopoietic growth factor treatment in chronic stroke in aged mice: a treatment frequency study Cell Transplant. Appeared or available on-line: January 26, 2016.
"These manuscripts from studies presented at the 22nd annual ASNTR meeting are representative of the excellent progress in neural therapy as well as the mission of the society itself," said Dr. Cesario V. Borlongan, president of the 23rd ASNTR, and Distinguished Professor at the Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL. "We look forward to hosting another successful annual meeting in which colleagues can share recent breakthroughs and advances in neural therapy for various neurological conditions."
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The 23rd ASNTR Annual Meeting will be held in Clearwater, Florida April 28-30, 2016. Contact Donna Morrison at dmorriso@health.usf.edu
The Coeditors-in-chief for CELL TRANSPLANTATION are at the Diabetes Research Institute, University of Miami Miller School of Medicine and Center for Neuropsychiatry, China Medical University Hospital, TaiChung, Taiwan. Contact, Camillo Ricordi, MD at ricordi@miami.edu or Shinn-Zong Lin, MD, PhD at shinnzong@yahoo.com.tw or David Eve, PhD or Samantha Portis, MS, at celltransplantation@gmail.com
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