Abstract
The 22nd annual meeting of the American Society for Neural Therapy and Repair (ASNTR) was held in Clearwater, Florida, on April 30–May 2, 2015. Esteemed members gathered to share their innovative approaches for neural therapy and repair and presentations were given on a myriad of topics such as new diagnostic tests, preventative medicine, stem cell therapy, and new biotechnology that may potentially be applied for treatment of a wide array of neurological disorders. This special ASNTR issue of Cell Transplantation features several articles that extrapolate the presented data and contribute significantly to the field.
The biological and pathological mechanisms underlying the analgesic effects of acupuncture, a practice used in traditional Chinese medicine, were theorized in a review by Lin et al. Acupuncture has been used effectively to treat various painful conditions in Eastern countries for thousands of years, but the physiological basis for the treatment is still a topic for conjecture. Many researchers have hypothesized that the therapeutic effect is rendered via immunoregulatory pathways and modulation of neurotransmitter activity. Here, the authors present the existing body of evidence that suggests inhibition of microglial activity may be responsible for the antinociceptive effects of acupuncture. Analgesia was further explored by Jergova et al. in their study using inhibitory GABAergic cells to treat neuropathic pain following an injury to the peripheral nerves. Currently, treatment of neuropathic pain is predominantly palliative in nature, and a more permanent solution is highly desirable. Researchers engineered recombinant GABAergic cells that released the peptide Serine1-histogranin (SHG) for amelioration of neuropathic pain in a murine model and found that their treatment was able to abrogate the hyperexcitable state of spinal neurons that results after injury. The findings reported here implicate dysfunctional GABAergic and glutamatergic signaling in the development of chronic neuropathic pain postinjury and suggest that targeting multiple pathways may result in a therapeutic outcome.
In the area of cell transplantation, Rossetti et al. sought to compare different suspensions of human neural stem cells (hNSCs) in an in vitro study in order to determine the optimal conditions for successful intracerebral transplantation. The mechanical and biophysical properties of five different vehicles were compared. The data from the in vitro study could be applied to improving the methodology employed to treat various neurological conditions with cell transplants. In a study by Lelos et al., cell suspensions dissociated from the whole ganglionic eminence of fetal rats (rWGE) and humans (hWGE) were transplanted into the striatum of adult rats modeled with Huntington's disease (HD). Both rWGE- and hWGE-transplanted rats showed significant improvement in motor function and behavior posttransplantation, suggesting that cells derived from this source (WGE) may indeed be beneficial for the treatment of HD, though further studies are warranted to assess the effects of WGE cell transplantation on cognition. Fink et al. chose to explore a different therapeutic approach for HD by transfecting human fibroblasts with transcription activator-like effectors (TALE) that would repress the allele associated with the disease, thus demonstrating that the mutant huntingtin gene could be targeted with specificity. Gene therapy has long been a part of the lexicon of biologists and medical researchers alike, but its clinical application has not yet been fully realized. This study could be a possible stepping-stone to furthering this technique.
Other studies investigated the use of stem cells derived from nonneural sources for the treatment of other neurodegenerative conditions, as in a study by Matchynski-Franks et al. in which mesenchymal stem cells (MSCs) were injected directly into the hippocampi and/or lateral ventricles of mice modeled with Alzheimer's disease (AD). MSCs have long been considered an excellent candidate for cell therapy due to their abundance in different adult tissues and relative ease of isolation. The results indicated that MSC transplantation reduced cognitive deficits, altered levels of pathological β-amyloid, and tempered inflammation.
In addition to neurodegenerative diseases, typical aging can also have an impact on cognition and motor function, as neurogenesis, the process by which new neural cells are generated, is significantly dampened as we age. Aging may often have a deleterious effect on the cardiovascular system as well, creating a milieu that increases the risk of ischemia. Liang et al. found that aging seemed to have a negative impact on regenerative processes and neural repair mechanisms; however, further studies comparing the rate of neurogenesis in poststroke hypertensive and normotensive rats are needed.
An additional three articles also investigated different repair mechanisms and therapeutic modalities following stroke. Obtulowicz et al. induced Wharton's jelly-derived MSCs (WJ-MSCs) to differentiate into endothelial-like progenitor cells (WJ-EPCs) in order to restore angiogenesis, a process by which new blood vessels are developed, and neurogenesis in an ex vivo model of stroke. The researchers concluded that both types of cells, WJ-MSCs and induced WJ-EPCs, can release soluble factors that are neuroprotective. The two remaining studies sought to characterize how soluble factors exert a therapeutic effect on the postischemic brain via paracrine effects.
One of the prevailing theories of the mechanisms behind successful cell transplantation is that transplanted cells, rather than being used to directly replace dying cells, can be used to stimulate the host microenvironment by releasing growth factors, cytokines, and other factors that are conducive to tissue regeneration, thereby activating endogenous repair processes. A study by Liu et al. aimed to ascertain whether hematopoietic growth factor treatment could reduce the production of a protein associated with the formation of blood clots and, subsequently, restore motor function. The results revealed a positive effect by paracrine mechanisms, while, conversely, a second study by Di Santo et al. revealed that treatment with EPC-conditioned medium also yielded positive outcomes for stroke that did not appear to be dependent upon growth factors or cytokines.
In summary, these articles provide a preponderance of new insights into neural repair mechanisms and expand upon the topics introduced at the 22nd annual meeting of the ASNTR. We would like to thank our members for their interest in publishing in the special issue. This year, we had a significant number of authors who wished to contribute; however, due to time constraints for publishing the issue in time for the annual meeting, we were not able to include some manuscripts. Therefore, we plan to publish the remaining articles in a future special ASNTR issue or section of Cell Transplantation. As we look forward to the 23rd ASNTR meeting, we would like to extend our sincere appreciation to our colleagues who contributed to the special issue and express our enthusiasm in welcoming new and veteran members. We look forward to seeing you in Clearwater, Florida, April 28–30, 2016.