Combination strategies for repair, plasticity, and regeneration using regulation of gene expression during the chronic phase after spinal cord injury

OBJECTIVE Secondary health conditions (SHCs) are long-term complications that frequently occur due to traumatic spinal cord injury (tSCI) and can negatively affect quality of life in this patient population. This study provides an overview of the associations between the severity and level of injury and the occurrence of SHCs in tSCI. METHODS A systematic search was conducted in PubMed and Embase that retrieved 44 studies on the influence of severity and/or level of injury on the occurrence of SHCs in the subacute and chronic phase of tSCI (from 3 months after trauma). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS In the majority of studies, patients with motor-complete tSCI (American Spinal Injury Association [ASIA] Impairment Scale [AIS] grade A or B) had a significantly increased occurrence of SHCs in comparison to patients with motor-incomplete tSCI (AIS grade C or D), such as respiratory and urogenital complications, musculoskeletal disorders, pressure ulcers, and autonomic dysreflexia. In contrast, an increased prevalence of pain was seen in patients with motor-incomplete injuries. In addition, higher rates of pulmonary infections, spasticity, and autonomic dysreflexia were observed in patients with tetraplegia. Patients with paraplegia more commonly suffered from hypertension, venous thromboembolism, and pain. CONCLUSIONS This review suggests that patients with a motor-complete tSCI have an increased risk of developing SHCs during the subacute and chronic stage of tSCI in comparison with patients with motor-incomplete tSCI. Future studies should examine whether systematic monitoring during rehabilitation and the subacute and chronic phase in patients with motor-complete tSCI could lead to early detection and potential prevention of SHCs in this population.

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Regenerative therapy for spinal cord injury using iPSC technology

Inflammation and Regeneration ◽

10.1186/s41232-020-00149-0 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Narihito Nagoshi ◽

Hideyuki Okano ◽

Masaya Nakamura

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Chronic Phase ◽

Regenerative Therapy ◽

Spinal Cord Regeneration ◽

Gamma Secretase ◽

Safety Issues ◽

Beneficial Effects ◽

Cord Injury ◽

Induced Pluripotent

Abstract Spinal cord injury (SCI) is a devastating event that causes permanent neurologic impairments. Cell transplantation therapy using neural precursor cells (NPCs) is a promising intervention aiming to replace damaged neural tissue and restore certain functions. Because the protocol to produce human induced pluripotent stem cells (iPSCs) was first established, we have attempted to apply this technology for regenerative therapy in SCI. Our group reported beneficial effects of iPSC-derived NPC transplantation and addressed safety issues on tumorigenicity after grafting. These findings will soon be tested at the clinical trial stage, the protocol of which has already been approved by the Ministry of Health, Labour and Welfare in Japan. Current transplantation therapies treat patients at the subacute phase after injury, highlighting the need for effective treatments for chronic SCI. We recently demonstrated the modest efficacy of gamma secretase inhibitor treatment of iPSC-NPCs before transplantation at the chronic phase. However, more comprehensive strategies involving combinatory therapies are essential to enhance current spinal cord regeneration treatments.

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