Abstract
We are very happy to announce that the publication of the first International Association of Neurorestoratology (IANR) section of Cell Transplantation has become true. This section will be a periodical specialty one dedicated to publishing important advancements in the preclinical research and clinical application of neurorestoratology in the future. It will open a window for popularizing neurorestoratology—a new distinct discipline—and spreading knowledge and information to enlighten more scientists and clinical physicians on this cutting-edge subject and share the advancements and experience in this new field.
In 2009, the Beijing Declaration of IANR clearly defined Neurorestoratology in detail; the concept, the research and scope, interventional therapies, discipline objective, developing direction, and the abiding principles (4). From neurorestoration to neurorestoratology, one common word became a special discipline term following the hard work of innumerable scientists and clinical physicians in this field; its birth stems from neuroscientific innovation and its development will involve cross-pollination with other disciplines and the meeting of specific challenges.
The core of Neurorestoratology is especially to restore the neurological functions of patients and improve their quality of life. We know there are a plethora of inspiring results in basic research which suggest that we can functionally restore damage to the CNS based on animal models of degenerative diseases and injury. Un-fortunately, the majority of physicians remain ignorant or unaware of these advances and insist on saying that there is currently no way to fulfill a patient's longing for treatment. We should not forget the Declaration of Helsinki, “in the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering” (9). Last, but not least, the need for functional neurorestoration is known by all; the cure is known by none. The cure lies in the future, but the seeds are in our hands, for us to plant; so translation between basic and clinic studies, comparison, integration, and the combination of current effective therapies must be carried out and clinical treatment guidelines should be made as fast as possible in order for patients to derive maximum benefit from the achievements and advancements being made in the field of Neurorestoratology.
It puzzles me greatly that many authors still state that there are no therapeutic methods to restore, even partially, neurological functions for intractable damage or diseases in the CNS within their articles when they de-scribe the current situation of this field, but in which they reported some functional restoration by their own methods. I wonder why they fear and deny the achievements of neurorestoratology from others while they state achieving positive results. If their statement is true, that is, there are no therapeutic methods to restore, even partially, neurological functions in basic and clinic studies, then we have not made any progress in this field except for lessons and the rest would be nonsense. Needless to say, this statement is false and unfair to all scientists and clinical physicians who have dedicated themselves to this field. Even if the advance is limited, should we not highlight and respect these achievements? Moreover, it is a common view in Neurorestoratology and the IANR that any small functional gains that have significant effects on a patient's quality of life should be recognized. Currently, with no doubt, it is an explicit conclusion that structural and functional restoration has been achieved to a certain extent in the CNS; however, at present the degree of neurological functional restoration is limited and far below many patients' higher expectation (3).
The randomizing double blind control study is a very important tool to assess effect in clinical trials. But it is not the only feasible tool; sometimes it even is unavailable for some treatment or studies, such as organ (heart, liver, and kidney) transplantation. It is believed that these diseases (heart failure, liver failure, and kidney failure) can only be treated by organ transplantation. In this condition, self-comparison as an assessment method is a much better tool than randomizing double blind control for ethical, lawful, and scientific reasons. Patients with complete chronic spinal cord injury (SCI) or deteriorated amyotrophic lateral sclerosis (ALS) are always told that there is no way and no chance to improve or restore their neurological functions in the same way as for patients with heart failure, liver failure, and kidney failure. The latter did not require cardiac surgeons, liver surgeons, and urology surgeons to do randomizing double blind control studies, and even did not require comparisons between treated patients and nontreated patients because self-comparison is the best way and the simplest tool to assess the effect of treatment for these kinds of diseases. Under the same conditions, surely this means that self-comparison to assess the effect of cell transplantation for complete chronic SCI or deteriorated ALS is the best and simplest tool to answer whether the treatment is effective. Therefore, Neurorestoratology and IANR openly and strongly support and encourage scientists and physicians by using the rational, reasonable, and practical research methods to do study, but not follow the mechanical, doctrinal, or rigid way.
In this special section of Cell Transplantation, several articles provide further evidence on the reality of neurorestoratology. Jamous et al. (5) used the Midi MACS magnetic separator to purify aspirated bone marrow in 33 mice and concluded that the purification of bone marrow stem cells based on the expression of either stem cell antigen-1 or Prominin-1 greatly increased the yield of astrocytes or neurons, respectively. Increasing data have shown that olfactory ensheathing cell (OEC)-based therapy is one of the most promising candidates in CNS neurorestorative strategy. Liu et al. (6) used shotgun proteomics to screen proteins from the plasma membrane and extracellular matrix proteins of rat OECs and identified a large number of proteins (168 nonredundant secreted proteins and 470 plasma membrane proteins), the majority of which have never been reported to be produced by rat OECs before. Shen et al. (8) fabricated silk fibroin scaffolds (SFS) as an extracellular matrix for OECs. The results of this study show that the diameter of the fiber plays an important role in guiding OEC adhesion, growth, and migration in vitro and the 300 nm SFS are suitable to construct tissue engineered scaffolds for SCI repair. Wu et al. (10) investigated the effect of transplanted OECs on retinal ganglion cells (RGCs) after intraorbital optic nerve (ON) transection in adult rats. It suggests that OEC transplantation induces the expression of brain-derived neurotrophic factor (BDNF) in the ocular ON stump and retina and delays the death of axotomized RGCs at a certain survival period. Transfection of the neurotrophin-3 (NT-3) gene into OECs and examination of the subsequent therapeutic effect of rat NT-3 gene-modified OEC transplantation on SCI was investigated by Ma et al. (7). The results show that genetically modified OECs are capable of surviving and producing a neurotrophic factor in vivo, which significantly improved the recovery after SCI. Bohbot (1) performed a double therapy of OEC transplantation combined with LASERPONCTURE® in three patients with chronic SCI, and the electromyography monitoring indicated some voluntary muscle activity was restored. A random controlled clinical trial involving the transplantation of OECs into 33 children and adolescents with cerebral palsy (CP) was performed by Chen et al. (2). Fourteen of these patients (six OECs treated and eight controls) completed the 6-month study and they demonstrated that OEC intracranial transplantation is an alternative treatment for CP.
This special section contributed by experts from IANR, with the important cooperation of Cell Transplantation, provides a platform of multidisciplinary academic exchange for basic and clinical research embraced by the discipline of Neurorestoratology. Focusing on the final clinical application, we welcome global contributors to submit your original research manuscripts, technique notes, reviews or minireviews, conceptual discussions, and position papers, etc. Fostering the belief that united nations are stronger than divided ones, let us meet the challenges together. Finally, I would like to express my sincere gratitude to the editors in chief and editorial board of this leading journal for their strong support.