Abstract
The 23rd annual meeting of the American Society for Neural Therapy and Repair (ASNTR) was held in Clearwater, Florida, from April 28 to 30, 2016. Leaders in groundbreaking research areas, including cell therapy and neuroregeneration, gathered to present their data and share their contributions with other leading experts and emerging scientists. With cell therapy as the focal point for the symposia, many attendees presented research on a variety of cell types, including mesenchymal stem cells (MSCs), amniotic stem cells, induced pluripotent stem cells (iPSCs), and neural progenitor (NP) cells for neurological disorders. This special ASNTR issue of Cell Transplantation comprises articles that report on advancements in cell therapy, detailing stem cell types, trophies, and immune factors that influence endogenous repair mechanisms, and new methods and technologies.
Stem cells and other immune-modulating cells can be derived from a variety of tissues and can be used in regenerative medicine to quell inflammatory sequelae. One rich source of therapeutic cells is the placenta, specifically the amniotic membrane (AM), from which amniotic epithelial cells and MSCs can be derived, as detailed in a review article by Silini et al. AM-derived cells may be useful in treating a plethora of conditions, such as intrauterine inflammation. Yawno et al. transplanted human amniotic epithelial cells (hAECs) into an ovine model of intrauterine inflammation. Researchers found that hAECs administered 24 h after exposure to an inflammatory insult protected against neuroinflammation and prevented the loss of white matter.
In addition to the transplantation of cells, researchers also provided data on methods designed to upregulate endogenous neurogenesis. Pu et al. found that a diet enriched with omega-3 polyunsaturated fatty acids (n-3 PUFAs) led to cognitive recovery after traumatic brain injury (TBI) in mice. Additionally, the authors noted that mice given an n-3 PUFA-rich diet had enhanced survival of neurons, increased generation of immature neurons, and increased angiogenesis and oligodendrogenesis. Neuroprotective, anti-inflammatory effects were also observed when Wu et al. treated rats modeled with ischemic stroke with CD549, a C-X-C chemokine receptor type 4 (CXCR4) antagonist. The authors noted that this treatment resulted in decreased activation of microglia, dampened expression of inflammatory markers, increased neuronal survival, increased mobilization of endogenous hematopoietic stem cells, and improved behavioral outcomes.
Ruzicka et al. compared the effectiveness of three different types of human cells for treating spinal cord injury (SCI). Rats modeled with SCI were transplanted with bone marrow-derived MSCs (BM-MSCs), NPs, or iPSC-derived NPs (iPSC-NPs). The iPSC-NP-transplanted group showed the greatest improvement in locomotor function, the greatest sparing of white and gray matter, and the lowest degree of inflammation. Yang et al. used neural progenitor cells to treat jaundiced rats and found that NPs protected vulnerable areas of the brain from inflammatory insults and that the grafted NPs also formed neurites, which could possibly lead to the formation of new, functional connections.
To that end, targeted cell delivery and tracking of transplanted cells were also important topics of last year's meeting. Vermilyea et al. developed a trajectory guide system for real-time intraoperative magnetic resonance imaging (RT-IMRI) to deliver iPSCs to a nonhuman primate. Postmortem analysis confirmed successful delivery and survival of grafted cells. Nicholls et al. evaluated the effectiveness of exogenous labels in tracking transplanted neural stem cells. The authors found that they were able to differentiate endogenous cells from grafted cells using these exogenous labels. Thus, the ability to reliably interpret the efficacy of cell transplantation may be further enhanced through accurate transplantation and tracking of the therapeutic cells.
In a phase I/IIa clinical trial, Syková et al. transplanted amyotrophic lateral sclerosis (ALS) patients with MSCs. The treatment was found to be safe and effective in slowing disease progression. The study may prove to be a launching pad for future studies using stem cells for neurodegenerative diseases. In addition to cell transplantation for ALS, researchers also studied other diseases and aspects of neurodegeneration. Parkinson's disease (PD) is characterized by a reduction of dopaminergic neurons in the striatum, leading to diminished locomotor ability and control. Baldwin et al. analyzed the gait of a murine model of PD and found that the step sequence was critical to gait analysis. These findings could contribute to the development of PD models that better mimic the human condition. Ferrazoli et al. found that purigenic signaling may be involved in the pathogenesis of PD. Treating a rat model of PD with P2X7R, a purigenic receptor antagonist, they found that PD symptoms were allayed and dopamine levels increased in the substantia nigra. Using a rat model of PD, Di Santo et al. showed that transplantation of serotonin-expressing fetal ventral mesencephalon-derived cells may be a viable treatment option. Alzheimer's disease (AD) is characterized by a dramatic loss of neural cells. Counts et al. found that the cell cycle may play a pivotal role in disease pathogenesis. The protein regulator of cell cycle (RGCC) may be highly dysfunctional in AD, and reversal of its stymied activity may lead to amelioration of the disease.
In summary, the articles herein provide a myriad of data from the 23rd ASNTR meeting on new frontiers in cell therapy and regenerative medicine for neurological disorders. I would like to extend my sincere gratitude to our contributors for making this special issue an accessible wealth of knowledge pertaining to cell therapy research. Moving forward, the 24th ASNTR meeting promises to nurture our colleagueship and bring further advancement to our field. I look forward to seeing you, once again, in sunny Clearwater, Florida, April 27-29, 2017.