Stem Cell-Based Therapies for Spinal Cord Injury

Tewarie, Rishi S. Nandoe; Hurtado, Andrés; Bartels, Ronald; Grotenhuis, André; Oudega, Martin

doi:10.1080/10790268.2009.11760761

Cited by 115 publications

(59 citation statements)

References 138 publications

(137 reference statements)

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“…Neural stem cells (NSCs) can differentiate into neurons, oligodendrocytes (OLs), and astrocytes, and are a promising candidate for cell transplantation to treat spinal cord injury (SCI) [1]. Recently, NSC-based therapy of SCI has been attempted in numerous animal experiments and produced encouraging results [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Shen

Wang

et al. 2012

Neurotherapeutics

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Neural stem cell (NSC) transplantation is a major focus of current research for treatment of spinal cord injury (SCI). However, it is very important to promote the survival and differentiation of NSCs into myelinating oligodendrocytes (OLs). In this study, myelin basic protein-activated T (MBP-T) cells were passively immunized to improve the SCI microenvironment. Olig2-overexpressing NSCs were infected with a lentivirus carrying the enhanced green fluorescent protein (GFP) reporter gene to generate Olig2-GFP-NSCs that were transplanted into the injured site to differentiate into OLs. Transferred MBP-T cells infiltrated the injured spinal cord, produced neurotrophic factors, and induced the differentiation of resident microglia and/or infiltrating blood monocytes into an "alternatively activated" anti-inflammatory macrophage phenotype by producing interleukin-13. As a result, the survival of transplanted NSCs increased fivefold in MBP-T cell-transferred rats compared with that of the vehicle-treated control. In addition, the differentiation of MBP-positive OLs increased 12-fold in Olig2-GFP-NSC-transplanted rats compared with that of GFP-NSC-transplanted controls. In the MBP-T cell and Olig2-GFP-NSC combined group, the number of OL-remyelinated axons significantly increased compared with those of all other groups. However, a significant decrease in spinal cord lesion volume and an increase in spared myelin and behavioral recovery were observed in Olig2-NSC-and NSC-transplanted MBP-T cell groups. Collectively, these results suggest that MBP-T cell adoptive immunotherapy combined with NSC transplantation has a synergistic effect on histological and behavioral improvement after traumatic SCI. Although Olig2 overexpression enhances OL differentiation and myelination, the effect on functional recovery may be surpassed by MBP-T cells.

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Section: Introductionmentioning

confidence: 99%

“…Recently, NSC-based therapy of SCI has been attempted in numerous animal experiments and produced encouraging results [1][2][3][4]. However, the studies also found that after transplantation into the injured spinal cord, most NSCs differentiate into astrocytes, but not OLs and neurons [5,6].…”

Section: Introductionmentioning

confidence: 99%

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Shen

Wang

et al. 2012

Neurotherapeutics

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“…Recent pathological studies have suggested that the difficulties of functional recovery after SCI mainly included the survival of cells, regeneration of axons, the precise location of regenerative axons, and accurate reformation and functional synaptic connections (Nandoe Tewarie et al, 2009). Because NSCs have the potential to differentiate into neurons (Lee et al, 2012), oligodendrocytes, and axons (Decimo et al, 2011;Yasuda et al, 2011) and also have the ability to fill the spinal cord cavity and blend with host spinal cord tissues (Boido et al, 2011;Li et al, 2011), they may be useful for repairing SCI.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair

et al. 2015

Genet. Mol. Res.

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ABSTRACT.We examined the effect of muscle basal lamina (MBL) with neural stem cells (NSCs) and olfactory ensheathing cells (OECs) on spinal cord injury repair. Seventy-two Sprague-Dawley rats were subjected to spinal cord hemisection and divided into 6 groups. In blank control group (group A), the ends of the spinal cord hemisection model were flushed with physiological saline. In NSC transplantation group (B), OEC transplantation group (C), MBL with NSC transplantation group (D), MBL with OEC transplantation group (E), and MBL with NSC and OEC transplantation group (F), NSCs, OECs, MBL with NSCs, MBL with OECs, and MBL with NSCs and OECs were implanted into the ends of the hemisection model. Survival and migration of transplanted cells were detected by immunohistochemistry and immunofluorescence after 4 and 8 weeks. Hind limb function repair was evaluated by Bundle branch block score at various time points before and after surgery. MBL could promote NSC growth along its lumen and promote host cell advancement in the lumen, reducing local inflammatory responses. Using MBL with NSCs 13438 X.W. Kang et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 13437-13455 (2015) and/or OECs for spinal cord repair shows advantages over simple cell transplantation. Group F contained more nerve cells in muscle basal lamina than group E. This method is useful for forming more axons, synaptic connections, and signal transduction pathways. However, these new axons showed nerve demyelination, which may greatly limit nerve signal conduction. In group F, OECs could induce neural stem cells, axonal growth, and synaptic connection formation, but its role is limited.

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“…Cell-based therapies using adult bone marrow-derived progenitor/stem cell technologies might also prove highly successful for the treatment of fibrosis [136][137][138]. Since fibrocytes and EMT-derived myofibroblasts produce a variety of factors that are involved in the fibrotic process recruitment and/or activation could provide a unique therapeutic approach to treat a variety of fibrotic diseases.…”

Section: An Overview On the Phenomena At Cellular Scalementioning

confidence: 99%

Towards a unified approach in the modeling of fibrosis: A review with research perspectives

Amar

Bianca

2016

Physics of Life Reviews

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Pathological fibrosis is the result of a failure in the wound healing process. The comprehension and the related modeling of the different mechanisms that trigger fibrosis is a challenge of many researchers that work in the field of medicine and biology. The modern scientific analysis of a phenomenon generally consists of three major approaches: theoretical, experimental, and computational. Different theoretical tools coming from mathematics and physics have been proposed for the modeling of the physiological and pathological fibrosis. However a complete framework is missing and the development of a general theory is required. This review aims at finding a unified approach in the modeling of fibrosis diseases that takes into account the different phenomena occurring at each level: molecular, cellular and tissue. Specifically by means of a critical analysis of the different models that have been proposed in the mathematical, computational and physical biology, from molecular to tissue scales, a multiscale approach is proposed, an approach that has been strongly recommended by top level biologists in the past decades.

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Stem Cell-Based Therapies for Spinal Cord Injury

Cited by 115 publications

References 138 publications

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair

Towards a unified approach in the modeling of fibrosis: A review with research perspectives

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