From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury

Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.

Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury

Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,

Genetically modified human umbilical cord blood cells as a promising strategy for treatment of spinal cord injury

Spinal cord injury （SCI） continues to be a pressing health and social problem. The injury leads to neuronal and glial cell death accompanied by degeneration of nerve fibers. There are currently no particularly effective treatments. SCI causes profound disabil- ity of people affected and has attracted increased attention in the international field of neuroregeneration. For the past two decades, much hope has been placed in cell therapies for the restoration of both structure and function of the injured spinal cord. Embryonic and neural stem cells, olfactory ensheathing cells, microglia-like cells, Schwann cells, mesenchymal stem cells.

Chronic complications of spinal cord injury

Spinal cord injury(SCI) is a serious medical condition that causes functional, psychological and socioeconomic disorder. Therefore, patients with SCI experience significant impairments in various aspects of their life. The goals of rehabilitation and other treatment approaches in SCI are to improve functional level, decrease secondary morbidity and enhance health-relatedquality of life. Acute and long-term secondary medical complications are common in patients with SCI. However, chronic complications especially further negatively impact on patients' functional independence and quality of life. Therefore, prevention, early diagnosis and treatment of chronic secondary complications in patients with SCI is critical for limiting these complications, improving survival, community participation and health-related quality of life. The management of secondary chronic complications of SCI is also important for SCI specialists, families and caregivers as well as patients. In this paper, we review data about common secondary longterm complications after SCI, including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. The purpose of this review is to provide an overview of risk factors, signs, symptoms, prevention and treatment approaches for secondary long-term complications in patients with SCI.

Editor's Choice—Application of tissue-engineered materials in the repair of spinal cord injury

The development of tissue-engineered technology brings hope to the treatment of spinal cord injury. Preparation of a tissue-engineered spinal cord stent with three-dimensional bionic structure has important value in the construction of tissue-engineered spinal cord and the repair of spinal cord injury. Acellular scaffolds can be produced with chemical extraction,

Stem cells for treatment of spinal cord injury

Three articles regarding the effects of （gene-modified） bone marrow mesenchymal stem cells transplantation for treatment of spina cord injury and the migration process and distribution of transplanted stem cells observed by in vivo magnetic resonance imaging tracking, providing experimental evidence for spinal cord injury treatment with stem cell transplantation were reported in Neural Regeneration Research. We hope that our readers find these papers useful to their research.

Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries

The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.