scholarly journals Application of developmental principles for spinal cord repair after injury

Author(s):  
Florentia Papastefanaki

The superiority of the mammalian central nervous system (CNS) among other vertebrates does not involve an advanced capacity for regeneration and any insult results to irreversible function loss. Spinal cord injury (SCI) is one example of CNS trauma affecting thousands of individuals, mostly young, each year. Despite enormous progress in our comprehension of the molecular and cellular mechanisms underlying the pathophysiology after SCI, also providing targets for therapeutic interventions, so far, no efficient therapy exists, emphasizing the necessity for further research. A breadth of studies have demonstrated that, after SCI, principles of development come at play either to promote or to prohibit spontaneous regeneration and their accurate manipulation holds promise toward functional recovery. In this overview, some of the most recent and important studies are discussed that offer explicitly novel input from the field of development to the field of CNS repair regarding the modification of the inhibitory environment of the injured spinal cord – majorly referring to the glial scar – the activation of endogenous cell populations such as ependymal stem cells and oligodendrocyte precursor cells, and the developmental transcriptional program that is transiently activated in neurons after injury. Furthermore, current advances in stem cell technology are highlighted in terms of refinement and precise design of the appropriate stem cell population to be transplanted not only for cell replacement but also for modulation of the host environment. As single-dimension applications were not yet clinically successful, combinatorial strategies tackling more than one targets are suggested as more auspicious.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3296
Author(s):  
Camila Marques de Freria ◽  
Erna Van Niekerk ◽  
Armin Blesch ◽  
Paul Lu

Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.


2014 ◽  
Vol 72 (6) ◽  
pp. 451-456 ◽  
Author(s):  
Eric Domingos Mariano ◽  
Chary Marquez Batista ◽  
Breno José Alencar Pires Barbosa ◽  
Suely Kazue Nagahashi Marie ◽  
Manoel Jacobsen Teixeira ◽  
...  

Spinal cord injury (SCI) and amyotrophic laterals sclerosis (ALS) are devastating neurological conditions that affect individuals worldwide, significantly reducing quality of life, both for patients and their relatives. Objective : The present review aims to summarize the multiple restorative approaches being developed for spinal cord repair, the use of different stem cell types and the current knowledge regarding stem cell therapy. Method : Review of the literature from the past 10 years of human studies using stem cell transplantation as the main therapy, with or without adjuvant therapies. Conclusion : The current review offers an overview of the state of the art regarding spinal cord restoration, and serves as a starting point for future studies.


Neurotrauma ◽  
2018 ◽  
pp. 431-444
Author(s):  
Ping Wu ◽  
Mingliang Yang ◽  
Yan Hao ◽  
Shiqing Feng ◽  
Jianjun Li

Traumatic spinal cord injury (SCI), a devastating disorder that severely affects the quality of life in patients, currently lacks effective therapies. Stem cell research offers a promising option to facilitate spinal cord repair. This chapter provides an overview of the major types of stem cells being used in preclinical animal studies and clinical trials to treat SCI, including mesenchymal, neural, hematopoietic, embryonic, and induced pluripotent stem cells. The authors summarize the beneficial effects of stem cells as a potential new therapeutic approach, but also raise the concerns of the limitation and challenges the field is facing, and suggest future directions.


2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.


2020 ◽  
Vol 32 (43) ◽  
pp. 2070325
Author(s):  
Letao Yang ◽  
Brian M. Conley ◽  
Susana R. Cerqueira ◽  
Thanapat Pongkulapa ◽  
Shenqiang Wang ◽  
...  

2021 ◽  
Author(s):  
Yixia Yin ◽  
Wenwu Wang ◽  
Qi Shao ◽  
Binbin Li ◽  
Dan Yu ◽  
...  

A IKVAV-functionalized hydrogel is developed. It not only enhances neural stem cell (NSC) attachment, growth, and differentiation, but also maintains the proliferation ability of the NSC spheroids in the hydrogel for spinal cord injury repair.


2016 ◽  
Vol 19 (4) ◽  
pp. 544-557 ◽  
Author(s):  
Thomas M. Fandel ◽  
Alpa Trivedi ◽  
Cory R. Nicholas ◽  
Haoqian Zhang ◽  
Jiadong Chen ◽  
...  

2000 ◽  
Vol 279 (6) ◽  
pp. C1677-C1684 ◽  
Author(s):  
Esther E. Dupont-Versteegden ◽  
René J. L. Murphy ◽  
John D. Houlé ◽  
Cathy M. Gurley ◽  
Charlotte A. Peterson

We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups ( n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation ( r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5′-Bromo-2′-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition.


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