Current status of experimental cell replacement approaches to spinal cord injury

Abstract

<jats:p>✓ Despite advances in medical and surgical care, the current clinical therapies for spinal cord injury (SCI) are largely ineffective. During the last 2 decades, the search for new therapies has been revolutionized by the discovery of stem cells, which has inspired scientists and clinicians to search for a stem cell–based reparative approaches to many diseases, including neurotrauma. In the present study, the authors briefly summarize current knowledge related to the pathophysiology of SCI, including the concepts of primary and secondary injury and the importance of posttraumatic demyelination. Key inhibitory obstacles that impede axonal regeneration include the glial scar and a number of myelin inhibitory molecules including Nogo. Recent advancements in cell replacement therapy as a therapeutic strategy for SCI are summarized. The strategies include the use of pluripotent human stem cells, embryonic stem cells, and a number of adult-derived stem and progenitor cells such as mesenchymal stem cells, Schwann cells, olfactory ensheathing cells, and adult-derived neural precursor cells. Although current strategies to repair the subacutely injured cord appear promising, many obstacles continue to render the treatment of chronic injuries challenging. Nonetheless, the future for stem cell–based reparative strategies for treating SCI appears bright.</jats:p>

Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial

“…Two physical therapists or physical medicine and rehabilitation physicians independently evaluated the preand postoperative (3,6,12,18, and 24 months) ASIA motor and sensory grades, including light touch and pinprick. These were recorded by a third party.…”

“…12,13,28 Therefore, aFGF may confer neuroprotection and create favorable conditions for axonal regeneration. Based on the findings here, future research should focus on verifying and maximizing the effects of aFGF while limiting side effects by adjustments in dosing and combinations with other strategies like cell replacement therapies 6,22 or lytic enzymes. …”

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

“…The limited success of pharmacologic treatment has shifted the focus of medical research away from these traditional treatments to other more promising areas such as cell-based therapy, particularly, the application of stem cell biology (Hipp and Atala, 2004;Stanworth and Newland, 2001). Thus, various cellular transplantation strategies have been utilized in different models of SCI (Eftekharpour et al, 2008). The adult spinal cord harbors endogenous stem/progenitor cells, collectively referred to as NPCs, which might be responsible for normal cell turnover.…”

Effect of Bone Marrow-derived Mesenchymal Stem Cells on Changes of Serum Levels of TNF-α and Locomotor Function after Spinal Cord Injury in Mice

“…The role of TNF-α is extended from the immune system to neuro-inflammatory in the nervous system (Leung and Cahill, 2010). Therefore, there is a need to improve functional recovery of spinal cord after injury including control of inflammation (Dyck et al, 2015), rescue of neural tissue (Kwon et al, 2013) stimulation of axonal regeneration by modulation of the lesioned environment (Eftekharpour et al, 2008) or promotion of remyelination (Gauthier et al, 2013).…”

“…The therapeutic interventions to promote neuronal regeneration may range from genetic modifications and stem cell transplantation to exogenous injection of neuroprotective factors (Tempel et al, 2015). A large number of studies were undertaken to determine the effects of transplanting a variety of stem cells or stem cell-derived cells in SCI using different strategies and approaches to address the glial scar and facilitate neuroanatomical plasticity (Eftekharpour et al, 2008;Karimi-Abdolrezaee and Eftekharpour, 2012;Alluin et al, 2014).…”