Cotransplantation of Mouse Neural Stem Cells (mNSCs) with Adipose Tissue-Derived Mesenchymal Stem Cells Improves mNSC Survival in a Rat Spinal Cord Injury Model

Oh, Jin Soo; Kh, Kim; An, Sung Su; Pennant, William A.; Kim, Hyo Jin; Gwak, So‐Jung; Yoon, Do Heum; Lim, Mi Hyun; Choi, Byung Hyune; Ha, Yoon

doi:10.3727/096368910x539083

Cited by 61 publications

(41 citation statements)

References 32 publications

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“…This novel strategy can be used to augment the therapeutic efficacy of combined stem cell and gene modulation therapy for SCI. In another study, Oh et al [63] , examined the effects of co-transplanting mouse neural stem cells (mNSCs) and adipose tissue-derived mesenchymal stem cells (ATMSCs) on mNSC viability. It was observed that mNSCs transplanted into rat spinal cords with AT-MSCs showed better survival rates than mNSCs transplanted alone, thereby suggesting that co-transplantation of mNSCs with AT-MSCs is a more effective strategy to improve the survival of transplanted stem cells into the injured spinal cord.…”

Section: Ratmentioning

confidence: 99%

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Dasari

Veeravalli

Dinh

2014

WJSC

184

144

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With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. Core tip: Despite our deeper understanding of the molecular changes that occurs after the spinal cord injury (SCI), the cure for paralysis remains elusive. In this review, the pathophysiology of SCI and characteristics and potential sources of mesenchymal stem cells (MSCs) that can be used in the treatment of SCI were discussed. We also discussed the progress of application of MSCs in research focusing on the neuroprotective properties of MSCs. Finally, we discussed the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

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Section: Ratmentioning

confidence: 99%

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Dasari

Veeravalli

Dinh

2014

WJSC

184

144

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“…This could then protect transplanted and possible host cells from the hypoxia. 7,8,28,29 Several elements, such as the hypoxia-responsive untranslated region, [30][31][32] oxygen-dependant degradation domain sequence, 33,34 RTP801 promoter 35 and Epo enhancer 31,36 have been used to design hypoxia-inducible systems. We have previously confirmed that the Epo enhancer-based system increases gene expression specifically in hypoxic cells.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

Kim

et al. 2011

Gene Ther

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO 2 , 1%) or a hypoxia-mimicking reagent (CoCl 2 ) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H 2 O 2 -induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.

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“…Guedes and colleagues also examine the possible therapeutic advantage of co-transplantation, acknowledging its beneficial effects towards cell survival. Recent trials show the delivery of neural stem cells combined with adipose-derived stem cells increased neural stem cell survival [2]. Overall, the article skillfully examines the potential of various stem cells, providing valuable background for future discovery.…”

Section: Bone Marrow-derived Stem Cellsmentioning

confidence: 99%

An update on stem cell therapy for neurological disorders: cell death pathways as therapeutic targets

et al. 2017

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Here, we compiled ten papers detailing recent strides in the field of stem cell therapy, which address critical issues relevant to pursuing this experimental treatment for clinical applications in brain disorders. Topics include efficacy, safety, and mechanism of action underlying cell therapy, emerging technologies and combination pharmacotherapies with cell transplantation directed at improving the functional outcomes, and evaluation of key translational components of advancing novel therapeutics to the clinic, including the need for vis-à-vis comparisons with the gold standard of treatment post-injury (i.e., physical rehabilitation). A bioethics paper is also incorporated here to further appreciate the current status of cell therapy in the community setting. The overall goal of this special volume is to provoke a meaningful assessment of the lessons we have learned in recent years and to use such knowledge to carefully translate safe and effective applications of cell therapy, and its mechanism of action for the treatment of neurological disorders.

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Cotransplantation of Mouse Neural Stem Cells (mNSCs) with Adipose Tissue-Derived Mesenchymal Stem Cells Improves mNSC Survival in a Rat Spinal Cord Injury Model

Cited by 61 publications

References 32 publications

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

An update on stem cell therapy for neurological disorders: cell death pathways as therapeutic targets

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