Clinical Trials of Stem Cell Treatment for Spinal Cord Injury

Abstract

There are more than one million patients worldwide suffering paralysis caused by spinal cord injury (SCI). SCI causes severe socioeconomic problems not only to the patients and their caregivers but also to society; therefore, the development of innovative treatments is crucial. Many pharmacological therapies have been attempted in an effort to reduce SCI-related damage; however, no single therapy that could dramatically improve the serious long-term sequelae of SCI has emerged. Stem cell transplantation therapy, which can ameliorate damage or regenerate neurological networks, has been proposed as a promising candidate for SCI treatment, and many basic and clinical experiments using stem cells for SCI treatment have been launched, with promising results. However, the cell transplantation methods, including cell type, dose, transplantation route, and transplantation timing, vary widely between trials, and there is no consensus regarding the most effective treatment strategy. This study reviews the current knowledge on this issue, with a special focus on the clinical trials that have used stem cells for treating SCI, and highlights the problems that remain to be solved before the widespread clinical use of stem cells can be adopted.

Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri‐mir‐375 to miR-375

“…while infections and vascular dysfunction are contributors to non-traumatic SCI [5]. More than one million patients around the world are paralyzed by SCI, which not only brings serious social and economic problems to patients and their families, but also to society [6]. Neuronal apoptosis is a key pathological feature of SCI [7].…”

Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion–compression model

“…Secondly, our strategy of intrathecal Shh-application required a second surgery which could not be performed early after SCI due to the reduced state of the animals and the increased risk of perioperative morbidity and complications. Thirdly, we had to optimize our intervention for possible translation into the clinical practice, requiring a stabilized situation and enough time to overcome logistical challenges [36]. The duration of the Shh-administration was subject to the protein's rapid clearance from the CNS as well its short-lived effects on a cellular level which require prolonged application with a constant concentration [19,37].…”

Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine

“…It is also evident that a combination of biomaterials with stem cell-derived neural cells adds further benefit to rehabilitation regimens (Harkema et al, 2011 ) along with spinal cord stimulation to drive neuroplasticity after transplantation (Formento et al, 2018 ). Human SCI clinical trials with cell-based therapies were recently reviewed (Silvestro et al, 2020 ; Yamazaki et al, 2020 ), along with a protocol in place for systematic review and meta-analysis of efficacy (Tang et al, 2020 ). An excellent report on the requirements for translation of stem cell therapies to the clinic for CNS repair including industry and regulatory considerations is provided by Aboody et al ( 2011 ).…”