Stem cell based therapies for spinal cord injury

Muheremu, Aikeremujiang; Jiang, Peng; Ao, Qiang

doi:10.1016/j.tice.2016.05.008

Cited by 62 publications

(55 citation statements)

References 61 publications

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“…although none of these approaches were sufficiently efficient to achieve axonal regeneration and to rewire the spinal cord after injury [4]. Although SCI treatment has always been a challenge for clinical practitioners and scientists, some progress has still been made, such as stem-cell-based therapies [5]. In addition, after SCI, the central nervous system fails to effectively reactivate developmental programs to rebuild novel circuitry to restore function [6].…”

Section: Introductionmentioning

confidence: 99%

Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

Peng¹,

Bo²,

Ding³

et al. 2017

Cell Physiol Biochem

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Aim: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. Methods: The rat model of SCI was established using Allen’s method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of β-catenin, Wnt3a, GSK-3β and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. Results: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the β-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3β and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. Conclusion: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

Peng¹,

Bo²,

Ding³

et al. 2017

Cell Physiol Biochem

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“…Stem cell-based therapy, including induced pluripotent, neural, and mesenchymal stem cells (MSCs), is considered to be a potential treatment for various diseases, such as stroke, spinal cord injury, idiopathic pulmonary fibrosis, malignant glioma, diabetes, and liver disease. [9][10][11][12][13][14][15][16] In recent years, some studies have reported the protective effects of adipose-derived MSCs (ADMSCs) in the experimental treatment of AKI. 17,18 Two types of adipose tissues (brown and white adipose) usually exist to maintain energy metabolism through the storage of lipids.…”

mentioning

confidence: 99%

Adipose‐derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia‐reperfusion in a rat model

Zhang

Wang

et al. 2017

Clin Exp Pharma Physio

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Acute kidney injury (AKI) represents a group of complicated syndromes with a high mortality rate. The administration of adipose-derived mesenchymal stem cells (ADMSCs) has been tested as a possible treatment method for AKI. The long-term evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal protection of ADMSCs are limited. In this study we have established a rat AKI model induced by IR and investigated the possible protective effects of ADMSCs. Adult Sprague-Dawley (SD) rats were divided into three groups (n = 6/each group). The MOCK group was as the normal control. Rats in the IR-AKI and IR-AKI+ADMSCs groups were subjected to IR injury by clamping both renal pedicles for 40 minutes. Rats in the MOCK and IR-AKI groups were injected with PBS via the tail vein as negative treatment controls. Rats in the IR-AKI+ADMSCs group received ADMSCs therapy (2 × 10 cells were injected into the rats via the tail vein). We found that ADMSC transplantation restored the pathologic morphology induced by IR-AKI to normal compared with the MOCK group, suggesting the reparative function of ADMSCs in kidney tissues. Compared with IR-induced AKI alone, ADMSC treatment significantly decreased the number of apoptotic cells, the level of total urinary protein and serum creatinine, the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ, TNF-α, IFN-γ, and TGF-β), and the inflammation-associated proteins (HGF and SDF1), but increased the expression of the anti-inflammatory cytokine, IL-10, and the anti-apoptotic regulator, Bcl-2. Our data have indicated that ADMSC transplantation may protect against IR-induced AKI by anti-apoptotic and anti-inflammatory effects.

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“…This facilitated cell survival and axonal regeneration. In general, it is accepted that combined treatment may be more effective [64][65][66] .…”

Section: Discussionmentioning

confidence: 99%

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

Yang

Zhang

et al. 2017

Acta Pharmacol Sin

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The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks posttransplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

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Stem cell based therapies for spinal cord injury

Cited by 62 publications

References 61 publications

Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

Adipose‐derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia‐reperfusion in a rat model

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

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