Viability-Dependent Promoting Action of Adult Neural Precursors in Spinal Cord Injury

Abstract

The aim of the study was the assessment of the effects of adult neural stem cell (NSC) transplantation in a mouse model of spinal cord injury (SCI). The contusion injury was performed by means of the Infinite Horizon Device to allow the generation of reproducible traumatic lesion to the cord. We administered green fluorescent-labeled (GFP-)NSCs either by intravenous (i.v.) injection or by direct transplantation into the spinal cord (intraspinal route). We report that NSCs significantly improved recovery of hind limb function and greatly attenuated secondary degeneration. The i.v. route of NSC administration yielded better recovery than the intraspinal route of administration. About 2% of total i.v.-administered NSCs homed to the spinal cord injury site, and survived almost undifferentiated; thus the positive effect of NSC treatment cannot be ascribed to damaged tissue substitution. The NSCs homing to the injury site triggered, within 48 h, a large increase of the expression of neurotrophic factors and chemokines. One wk after transplantation, exogenous GFP-NSCs still retained their proliferation potential and produced neurospheres when recovered from the lesion site and cultured in vitro. At a later time, GFP-NSC were phagocytated by macrophages. We suggest that the process of triggering the recovery of function might be strongly related to the viability of GFP-NSC, still capable ex vivo of producing neurospheres, and their ability to modify the lesion environment in a positive fashion.

Human Schwann cells exhibit long‐term cell survival, are not tumorigenic and promote repair when transplanted into the contused spinal cord

“…In experimental studies, cell therapeutics have been one of the approaches at the forefront of strategies aimed at promoting SCI repair. The introduction of a diversity of cell types, including Schwann cells (SCs) (Bamber et al, ; Barakat et al, ; Ghosh et al, ; Guest, Rao, Olson, Bunge, & Bunge, ; Paino and Bunge, ; Pearse et al, ; Schaal et al, ; Takami et al, ; Xu, Chen, Guenard, Kleitman, & Bunge, ; Xu, Guenard, Kleitman, Aebischer, & Bunge, ; Xu, Guenard, Kleitman, & Bunge, ; Xu, Zhang, Li, Aebischer, & Bunge, ), neural stem cells (NSCs) (Bottai, Madaschi, Di Giulio, & Gorio ; Cao et al, ; Karimi‐Abdolrezaee, Eftekharpour, Wang, Morshead, & Fehlings, ; Ogawa et al, ; Parr et al, ; Ziv, Avidan, Pluchino, Martino, & Schwartz, ), olfactory ensheathing cells (OECs) (Cao et al, ; Kubasak et al, ; Munoz‐Quiles, Santos‐Benito, Llamusi, & Ramon‐Cueto, ; Ramon‐Cueto, Cordero, Santos‐Benito, & Avila, ), mesenchymal stem cells (MSCs) (Cizkova, Rosocha, Vanicky, Jergova, & Cizek ; Kim, Oh, Lee, & Yoon ; Parr, Tator, & Keating, ), and bone marrow stromal cells (BMSCs) (Chiba et al, ; Fan, Du, Cheng, Peng, & Liu ; Neuhuber, Timothy Himes, Shumsky, Gallo, & Fischer, ; Ohta et al, ; Parr et al, ; Zurita and Vaquero, ), among others, have been reported independently to provide varying levels of improvement in tissue preservation, axon growth support, remyelination repair and axon conduction as well as functional recovery in animal models. However, unwanted side effects including the development of neuropathic pain (Hofstetter et al, ; Lang et al, ; Macias et al, ), and tumorgenicity (Lee, Tang, Rao, Weissman, & Wu, ) have been reported with cell transplants in some experimental paradigms.…”

Current Advances in Intravascular Administration of Stem Cells for Neurological Diseases: A New Dose of Rejuvenation Injected

“…Importantly, to the best of my knowledge, every publication that reported successful cell homing and performed behavioral and motor test reported significant positive outcomes-decreased tissue damage and/or improved health condition scores compared to untreated animals. Among numerous diseases studied, the most prominent examples include stroke, 3 spinal cord injury, 4 and amyotrophic lateral sclerosis. 2 Notably, although the IV approach yields rather low rates of cell homing (0.0005-10% of injected cells found in the CNS), cells that migrated to the brain acquired identical phenotypes regardless of administration route.…”

The crosstalk between glycosphingolipids and neural stem cells

“…Only at the end of the last century were NSCs found to be present in mammals (Reynolds and Weiss ; Bottai et al . , ; Givogri et al . ; Adami et al .…”

“…From then on, new possibilities of therapeutic approaches were imagined using these cells, hypothesizing their use in different neurological pathologies such as spinal cord injury, spinal muscular atrophy, amyotrophic lateral sclerosis, and Parkinson's disease (Bottai et al . , ; Pluchino et al . ; Corti et al .…”

“…Then, lower vertebrates were found to possess regenerative capacity in the central nervous system (CNS) particularly birds during the song learning phase (Alvarez-Buylla et al 1990). Only at the end of the last century were NSCs found to be present in mammals (Reynolds and Weiss 1992;Bottai et al 2003Bottai et al , 2008Givogri et al 2008;Adami et al 2018). From then on, new possibilities of therapeutic approaches were imagined using these cells, hypothesizing their use in different neurological pathologies such as spinal cord injury, spinal muscular atrophy, amyotrophic lateral sclerosis, and Parkinson's disease (Bottai et al 2003Pluchino et al 2003;Corti et al 2007;Daniela et al 2007;Givogri et al 2008;Adami et al 2014).…”