Improving the therapeutic efficacy of neural progenitor cell transplantation following spinal cord injury

Abstract

Introduction There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functional improvement following spinal cord injury (SCI). The authors discuss the challenges of NPC transplantation with respect to different populations of NPCs of glial and neuronal lineages, the timing of treatment relative to acute and chronic injury, and the progress in ongoing clinical trials. Expert commentary Preclinical research will continue to elucidate mechanisms of recovery associated with NPC transplants, including increasing the partnership with related fields such as spinal atrophies and multiple sclerosis. The clinical trials landscape will grow and include both acute and chronic SCI with increased partnership and strengthened communication between biotechnology, government and academia. There will also be growing effort to develop better biomarkers, imaging and outcome measures for detailed assessment of neurological function and measures of quality of life.

Restoring Motor Neurons in Spinal Cord Injury With Induced Pluripotent Stem Cells

“…Neither acute nor chronic stem cell transplants have yet been largely successful due mainly to the early inflammatory response, which is particularly damaging to cell grafts, and formation of the glial scar, which inhibits axonal regrowth. Thus, transplants occurring during the subacute phase, considered the optimal timeframe, have been shown to be more effective (Nishimura et al, 2013; Cheng et al, 2017; Lane et al, 2017; Nori et al, 2017). In the subacute phase, M2 macrophages, which have immune-mediating characteristics, are recruited to mitigate inflammation.…”

“…For these reasons, the transplantation of specific iPSC-derived MN subtypes into SCI lesions is currently untenable. The significant progress made in deriving individual MN subtypes from iPSCs remains subject to discovering novel methods of supporting post-mitotic MN survival in the unfavorable microenvironment of SCI (Davis-Dusenbery et al, 2014; Iyer et al, 2017; Lane et al, 2017). Because MN subtypes have differential vulnerabilities in SCI, targeting individual MN subpopulations is critical to developing effective, personalized treatments for SCI.…”

The Neuroplastic and Therapeutic Potential of Spinal Interneurons in the Injured Spinal Cord

“…Thus, the present discussion focuses on the transplantation of neuronal precursor cells with the goal of delivering new populations of SpINs to the injured spinal cord (Figure 3) (reviewed in [85]). Transplantation of neural precursor cells obtained from i) acutely dissected fetal spinal cord tissue (FSC), ii) FSC’s more selected in vitro expanded counterpart (lineage restricted neural progenitor cells (NPCs) devoid of extracellular and non-neural components), or iii) even neural stem cells, have been shown to survive, integrate with the injured adult spinal cord, and alter functional outcome (reviewed in [83, 85–88]). Despite the therapeutic benefit seen with transplantation, some caveats remain [78] (reviewed in [85]).…”

Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord

“…We hypothesized that these precursors would serve as a substrate to restore input to phrenic motoneurons caudal to injury. [21][22][23] In this study, a suspension of dissociated E13-E14 fetal spinal cord (FSC) tissue was transplanted into the injury cavity 1 week after a lateralized cervical (C3/4) contusion. Previous work in this field has consistently demonstrated the ability for FSC tissue to survive, proliferate, and integrate with host tissue when transplanted after a SCI.…”