Stem Cell Injection in the Hindlimb Skeletal Muscle Enhances Neurorepair in Mice with Spinal Cord Injury

Cruz-Martinez, Pablo; Pastor, Diego; Estirado, Alicia; Pacheco-Torres, Jesús; Jones, Jimmy

doi:10.2217/rme.14.38

Cited by 11 publications

(9 citation statements)

References 52 publications

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“…The approach used was similar to previously published reports. 17 , 66 Six-week-old C57BL/6 mice were given a diet with 0.2% cuprizone (w/w) (Sigma-Aldrich, St. Louis, MO, USA) for 12 weeks ad libitum in order to obtain a chronic version of toxicity-induced demyelination. Finely powdered cuprizone was mixed in the rodent chow and administered to the mice using specially designed feeders.…”

Section: Methodsmentioning

confidence: 99%

“…The isolation and culture of MSCs was performed as in our previous studies. 17 , 66 , 67 , 68 , 69 Briefly, the bone marrows of either transgenic GFP mice or C57BL/6 wild-type were extracted, disaggregated and cultured in plastic flasks. The following culture medium was used: Dulbecco's modified Eagle's medium (DMEM), (High Glucose) with GlutaMAX (BD Bioscience, San Diego, CA, USA), 15% fetal bovine serum (Biochrom, Berlin, Germany) and 1% penicillin/streptomycin (Gibco, Life Technologies, Baisley, UK).…”

Section: Methodsmentioning

confidence: 99%

“…The method used was similar to our previously published work. 66 , 68 Briefly, mice were injected with MSCs pre-cultured with 7 μ g/ml of Feraspin XL (Viscover, Miltenyi Biotec, Cologne, Germany). This allowed their detection using MRI.…”

Section: Methodsmentioning

confidence: 99%

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Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

et al. 2016

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Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

et al. 2016

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“…All methods for stem cell transplantation (intravenous, intrathecal, intramedullary, intranasal or skeletal muscle injection ) are based on the homing effect, the ability of implanted stem cells to move to the injured area [170][171][172][173][174][175][176][177][178][179][180]. Mesenchymal progenitor cells have been injected intravenously in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection.…”

Section: Mode Of Injectionmentioning

confidence: 99%

“…The intranasal delivery of bone marrow stromal cells to spinal cord lesions has been successfully tried out [176]. Stem cell injection in the hindlimb skeletal muscle has enhanced neurorepair in mice with spinal cord injury [178].…”

Section: Mode Of Injectionmentioning

confidence: 99%

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

Amr¹

2017

Mesenchymal Stem Cells - Isolation, Characterization and Applications

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We have aimed at distinguishing obligatory prerequisites for mesenchymal stem cell transplantation in spinal cord injury from those prerequisites which are unnecessary or are prerequisites that have to be further investigated. Obligatory prerequisites include the following. First, the site of injury is extensively gliotic, constituting an unsuitable medium for stem cell transplantation. It has to be dissolved by neurolyzing agents, chondroitinase ABC as an example. Second, stem cells need a suitable biomaterial scaffold for their proper integration. Third, the biomaterial scaffold necessitates a tissue filler harboring stem cells, other cells and neurotrophic factors in a combinatorial approach. Fourth, the efficiency of mesenchymal stem cells themselves has to be increased (by reducing oxidative stress-induced apoptosis, by hypoxic preconditioning, by modulating the extracellular matrix and by other measures). Prerequisites that have to be further investigated include the ideal source, mode, quantity, time point and number of injections of mesenchymal stem cells; which growth factors and cells to be used in the combinatorial approach; transforming mesenchymal stem cells into motor neuron-like cells or Schwann cells; increasing the homing effect of stem cells and how to establish a continuous drug and cell delivery system.

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Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone‐induced demyelination model

Barati

Kashani

Moradi

et al. 2019

J of Cellular Biochemistry

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Microglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real-time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg-1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1-specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg-1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS + cells), but M2 marker (Arg-1 + cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells. K E Y W O R D S cuprizone model, immunomodulation, mesenchymal stem cells, microglial phenotype, multiple sclerosis J Cell Biochem. 2019;120:13952-13964. wileyonlinelibrary.com/journal/jcb 13952 |

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Stem Cell Injection in the Hindlimb Skeletal Muscle Enhances Neurorepair in Mice with Spinal Cord Injury

Abstract: Bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates spinal cord repair in acute spinal cord lesions.

Cited by 11 publications

References 52 publications

Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone‐induced demyelination model

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