scholarly journals CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury

2020 ◽  
Vol 95 (2) ◽  
pp. 406-414 ◽  
Author(s):  
Mohamad Bydon ◽  
Allan B. Dietz ◽  
Sandy Goncalves ◽  
F M Moinuddin ◽  
Mohammed Ali Alvi ◽  
...  
2020 ◽  
Vol 29 ◽  
pp. 096368972092898
Author(s):  
Agata Przekora ◽  
Lukasz Juszkiewicz

Spinal cord injury (SCI) is considered as one of the most problematic neurological conditions requiring specialized clinical intervention. Taking into account that SCI is characterized by extensive loss of nerve cells, stem cell–based therapy seems to be a reasonable modern strategy to the treatment of SCI. The presented case report describes for the first time experimental treatment with the use of autologous adipose tissue–derived mesenchymal stem cells (ADSCs) of the chronic posttraumatic SCI in a domestic ferret patient with paresis of back legs. It should be noted that most reports in the available literature concern ADSC-based therapies for acute or subacute SCI treatment in other species. Application of ADSC-based therapy did not cause any adverse reactions and resulted in significant improvement of neurological and motor functions. Based on these outcomes, it may be concluded that this form of therapy is promising and may be potentially translated into clinical veterinary practice.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
E. Oliveira ◽  
R. C. Assunção-Silva ◽  
O. Ziv-Polat ◽  
E. D. Gomes ◽  
F. G. Teixeira ◽  
...  

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles—secretome—that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.


2021 ◽  
Author(s):  
Tsung-Cheng Yin ◽  
Pei-Lin Shao ◽  
Kuan-Hung Chen ◽  
Kun-Chen Lin ◽  
John Y. Chiang ◽  
...  

Abstract Background: This study tested whether combined hyperbaric oxygen (HBO) and allogenic adipose-derived mesenchymal stem cells (ADMSCs) would be superior to either one for improving the neurological function in rat after acute traumatic spinal cord injury (TSCI) in rat. Methods and Results: Adult-male SD rats (n=40) were equally categorized into group 1 (sham-operated control), group 2 (TSCI), group 3 (TSCI + HBO for 1.5h/day for 14 consecutive days after TSCI), group 4 (TSCI + ADMSCs/1.2x106 cells by intravenous injection at 3h and days 1/2 after TSCI) and group 5 (TSCI + HBO + ADMSCs), euthanized and spinal-cord tissue was harvested by day 49 after TSCI. The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2), inflammatory-signaling (TLR-4/MyD88/IL-1ß/TNF-α/substance-p), cell-stress signaling (PI3K/p-AKT/p-mTOR) and the voltage gated sodium channel (Nav1.3/1.8/1.9) biomarkers were highest in group 2, lowest in group 1 and significantly lower in group 5 than in groups 3/4 (all p<0.0001), but they did not differ between groups 3/4. The spinal cord-damaged area, the cellular levels of inflammatory/DNA-damaged (CD68+/GFAP+/γ-H2AX+ cells), MAPK family biomarkers (p-P38/p-JNK/p-ERK1/2) and cellular expressions of voltage gated sodium channel (Nav.1.3, Nav.1.8 and Nav.1.9 in NF200+ cells) as well as the pain facilitated cellular expressions (p-P38+/peripherin+ cells, p-JNK+/peripherin+ cells, p-ERK/NF200+ cells) exhibited an identical pattern of inflammation, whereas the neurological integrity displayed an opposite pattern of inflammation among the groups (all p<0.0001). Conclusion: Combined HBO-ADMSCs therapy offered additional benefits for protecting the neurological architectural and functional integrity against acute TSCI.


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