scholarly journals Therapeutic Potential of Paracrine Factors and Secretome-based Treatment in Spinal Cord Injury

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.


2021 ◽  
Vol 14 (8) ◽  
pp. 792
Author(s):  
Seong-Jun Kim ◽  
Wan-Kyu Ko ◽  
Gong-Ho Han ◽  
Daye Lee ◽  
Yuhan Lee ◽  
...  

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.


2016 ◽  
Vol 3 (04) ◽  
pp. 144 ◽  
Author(s):  
Hau Thi-My Lam ◽  
Minh Nguyen-Thu Tran ◽  
Khoa Anh Bui ◽  
Thao Thi-Thu Le ◽  
Khanh Hong-Thien Bui ◽  
...  

Introduction: Stem cell therapy is one of the most promising therapies for degenerative diseases and related injuries. Adipose tissue derived stem cells (ADSCs) exhibit some particular properties such as high production of paracrine factors. Indeed, ADSCs have been successfully used to treat diseases, including osteoarthritis, diabetic ulcer, etc. Methods: In this study, ADSCs were used to treat spinal cord injury (SCI) in a mouse model. Non-expanded ADSCs, from stromal vascular fractions (SVFs) isolated from both autologous and allogeneic adipose tissues, were injected into injured sites of mice at a specified dose. The SCI mouse model were generated by transection of spinal cord at vertebrae T8 - T10. After 1 week of transection, mice exhibiting completed SCI were divided into 4 groups: group 1 was control (mice without any treatment), group 2 was placebo (mice treated with platelet rich plasma (PRP)), group 3 was allogeneic SVF transplantation (mice treated with allogeneic SVFs), and group 4 was autologous SVF transplantation (mice treated with autologous SVFs). For the treatment groups, mice were transplanted with 20 µL of activated PRP or/and with 106 cells of SVF (allogeneic or autologous) into the injured position through laminectomy. The recovery of SCI was evaluated by locomotor test, sensory test and sensory-motor test at 5 weeks after transplantation. The histology of the spinal cord also was checked after 5 weeks. Results: The results showed that in all groups with PRP injected with or without SVFs, the inflammation was efficiently controlled. The glial scar as well as myelin defragmentation were clearly reduced. However, a significant improvement of BBB score was only recorded in mice transplanted with autologous SVFs. Conclusion: The results of our study show that autologous SVF transplantation in combination with PRP can be a promising therapy for SCI.


Spinal Cord ◽  
2016 ◽  
Vol 54 (10) ◽  
pp. 785-797 ◽  
Author(s):  
H E Marei ◽  
A Althani ◽  
S Rezk ◽  
A Farag ◽  
S Lashen ◽  
...  

2020 ◽  
Vol 21 (11) ◽  
pp. 4185
Author(s):  
Ju-Ro Lee ◽  
Jae Won Kyung ◽  
Hemant Kumar ◽  
Sung Pil Kwon ◽  
Seuk Young Song ◽  
...  

Due to the safety issues and poor engraftment of mesenchymal stem cell (MSC) implantation, MSC-derived exosomes have been spotlighted as an alternative therapy for spinal cord injury (SCI). However, insufficient productivity of exosomes limits their therapeutic potential for clinical application. Moreover, low targeting ability of unmodified exosomes is a critical obstacle for their further applications as a therapeutic agent. In the present study, we fabricated macrophage membrane-fused exosome-mimetic nanovesicles (MF-NVs) from macrophage membrane-fused umbilical cord blood-derived MSCs (MF-MSCs) and confirmed their therapeutic potential in a clinically relevant mouse SCI model (controlled mechanical compression injury model). MF-NVs contained larger quantity of ischemic region-targeting molecules compared to normal MSC-derived nanovesicles (N-NVs). The targeting molecules in MF-NVs, which were derived from macrophage membranes, increased the accumulation of MF-NVs in the injured spinal cord after the in vivo systemic injection. Increased accumulation of MF-NVs attenuated apoptosis and inflammation, prevented axonal loss, enhanced blood vessel formation, decreased fibrosis, and consequently, improved spinal cord function. Synthetically, we developed targeting efficiency-potentiated exosome-mimetic nanovesicles and present their possibility of clinical application for SCI.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ping Li ◽  
Zhao-Qian Teng ◽  
Chang-Mei Liu

Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes’ expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.


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