Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation

Rossignol, Julien; Boyer, Cinda M.; Thinard, Reynald; Remy, SÃ©verine; Dugast, Anne‐Sophie; Dubayle, David; Dey, Nicolas D.; Boeffard, FranÃ§oise; Delecrin, JoÃ«l; Heymann, Dominique; Vanhove, Bernard; Anegón, Ignacio; Naveilhan, Philippe; Dunbar, Gary; Lescaudron, Laurent

doi:10.1111/j.1582-4934.2009.00657.x

Cited by 53 publications

(64 citation statements)

References 57 publications

(52 reference statements)

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“…Coronal sections were cut on a cryostat (Vibrotome UltraPro 5000; Sim Co Ltd, Denizli, Turkey) at 30 μm and were mounted on positive charged microscope slides (Globe Scientific Inc, Paramus, NJ, USA). The tissue was labeled, using previously established free-floating fluorescent staining protocols [27] using antibodies for neuronal nuclei (mouse NeuN; 1/500, Abcam) and glial fibrillary acidic protein (rabbit GFAP; 1/500, Abcam). For immunohistochemical analysis, the tissue was first blocked using 10% normal goat serum in PBS with 0.1% Triton-X (Sigma) for 45 minutes at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis

et al. 2013

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IntroductionHuntington’s disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat on the short arm of chromosome 4 resulting in cognitive decline, motor dysfunction, and death, typically occurring 15 to 20 years after the onset of motor symptoms. Neuropathologically, HD is characterized by a specific loss of medium spiny neurons in the caudate and the putamen, as well as subsequent neuronal loss in the cerebral cortex. The transgenic R6/2 mouse model of HD carries the N-terminal fragment of the human HD gene (145 to 155 repeats) and rapidly develops some of the behavioral characteristics that are analogous to the human form of the disease. Mesenchymal stem cells (MSCs) have shown the ability to slow the onset of behavioral and neuropathological deficits following intrastriatal transplantation in rodent models of HD. Use of MSCs derived from umbilical cord (UC) offers an attractive strategy for transplantation as these cells are isolated from a noncontroversial and inexhaustible source and can be harvested at a low cost. Because UC MSCs represent an intermediate link between adult and embryonic tissue, they may hold more pluripotent properties than adult stem cells derived from other sources.MethodsMesenchymal stem cells, isolated from the UC of day 15 gestation pups, were transplanted intrastriatally into 5-week-old R6/2 mice at either a low-passage (3 to 8) or high-passage (40 to 50). Mice were tested behaviorally for 6 weeks using the rotarod task, the Morris water maze, and the limb-clasping response. Following behavioral testing, tissue sections were analyzed for UC MSC survival, the immune response to the transplanted cells, and neuropathological changes.ResultsFollowing transplantation of UC MSCs, R6/2 mice did not display a reduction in motor deficits but there appeared to be transient sparing in a spatial memory task when compared to untreated R6/2 mice. However, R6/2 mice receiving either low- or high-passage UC MSCs displayed significantly less neuropathological deficits, relative to untreated R6/2 mice.ConclusionsThe results from this study demonstrate that UC MSCs hold promise for reducing the neuropathological deficits observed in the R6/2 rodent model of HD.

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Section: Methodsmentioning

confidence: 99%

“…Our previous work suggested that reducing the number of cell passages may increase transplant survivability in rat bone-marrow MSCs and increase their efficacy in reducing behavioral deficits in the 3-nitropropionic acid rat model of HD [27]. …”

Section: Introductionmentioning

confidence: 99%

Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis

et al. 2013

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“…Despite the overexpression of SDF-1␣ by MSCs in this study, no significant differences in the inflammatory marker, IBA-1, was found between groups. As MSCs have been known to exert moderate, anti-inflammatory effects, it may be possible that the anti-inflammatory cytokines produced by the MSCs partially attenuated any increase in inflammation that would have otherwise occurred by introducing SDF-1␣ alone (Rossignol et al, 2009).…”

Section: An Stewart Et Al / Sdf-1 Overexpression By Mesenchymal Stmentioning

confidence: 99%

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Stewart

Matyas

Welchko

et al. 2017

RNN

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Abstract.Purpose: Utilizing genetic overexpression of trophic molecules in cell populations has been a promising strategy to develop cell replacement therapies for spinal cord injury (SCI). Over-expressing the chemokine, stromal derived factor-1 (SDF-1␣), which has chemotactic effects on many cells of the nervous system, offers a promising strategy to promote axonal regrowth following SCI. The purpose of this study was to explore the effects of human SDF-1␣, when overexpressed by mesenchymal stem cells (MSCs), on axonal growth and motor behavior in a contusive rat model of SCI. Methods: Using a transwell migration assay, the paracrine effects of MSCs, which were engineered to secrete human SDF-1␣ (SDF-1-MSCs), were assessed on cultured neural stem cells (NSCs). For in vivo analyses, the SDF-1-MSCs, unaltered MSCs, or Hanks Buffered Saline Solution (vehicle) were injected into the lesion epicenter of rats at 9-days post-SCI. Behavior was analyzed for 7-weeks post-injury, using the Basso, Beattie, and Bresnahan (BBB) scale of locomotor functions. Immunohistochemistry was performed to evaluate major histopathological outcomes, including gliosis, inflammation, white matter sparing, and cavitation. New axonal outgrowth was characterized using immunohistochemistry against the neuron specific growth-associated protein-43 (GAP-43). Results:The results of these experiments demonstrate that the overexpression of SDF-1␣ by MSCs can enhance the migration of NSCs in vitro. Although only modest functional improvements were observed following transplantation of SDF-1-MSCs, a significant reduction in cavitation surrounding the lesion, and an increased density of GAP-43-positive axons inside the SCI lesion/graft site were found. Conclusion:The results from these experiments support the potential role for utilizing SDF-1␣ as a treatment for enhancing growth and regeneration of axons after traumatic SCI. Research HighlightsMSCs were engineered to overexpress SDF-1␣. SDF-1␣ expression by MSCs enhances the migration of NSCs in vitro. SDF-1␣ expression by MSCs enhanced GAP-43 fibers within the lesion center.

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“…However, studies conducted in experimental animals indicate that allogeneic MSCs trigger donor-specific cellular and humeral immune responses in vivo . For example, pre-clinical studies conducted in rodents (Camp et al, 2009; Eliopoulos et al, 2005; Rossignol et al, 2009; Sudres et al, 2006), swine (Poncelet et al, 2007), equine (Pigott et al, 2013) and non-human primates (Isakova et al, 2010; Isakova et al, 2014) demonstrate that allogeneic MSCs induce measurable anti-donor T and B cell mediated responses. Indeed, the detection of donor-specific antibodies in the serum of transplant recipients provides clear evidence of allo-antigen recognition by B cells.…”

Section: Recent Advances In Msc Biology and Consequence For Neurodmentioning

confidence: 99%

Mesenchymal stem cells as cellular vectors for pediatric neurological disorders

Phinney

Isakova

2014

Brain Research

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Lysosomal storage diseases are a heterogeneous group of hereditary disorders characterized by a deficiency in lysosomal function. Although these disorders differ in their etiology and phenotype those that affect the nervous system generally manifest as a profound deterioration in neurologic function with age. Over the past several decades implementation of various treatment regimens including bone marrow and cord blood cell transplantation, enzyme replacement, and substrate reduction therapy have proved effective for managing some clinical manifestations of these diseases but their ability to ameliorate neurologic complications remains unclear. Consequently, there exists a need to develop alternative therapies that more effectively target the central nervous system. Recently, direct intracranial transplantation of tissue-specific stem and progenitor cells has been explored as a means to reconstitute metabolic deficiencies in the CNS. In this chapter we discuss the merits of bone marrow-derived mesenchymal stem cells (MSCs) for this purpose. Originally identified as progenitors of connective tissue cell lineages, recent findings have revealed several novel aspects of MSC biology that make them attractive as therapeutic agents in the CNS. We relate these advances in MSC biology to their utility as cellular vectors for treating neurologic sequelae associated with pediatric neurologic disorders.

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Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation

Cited by 53 publications

References 57 publications

Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis

Transplantation of umbilical cord-derived mesenchymal stem cells into the striata of R6/2 mice: behavioral and neuropathological analysis

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Mesenchymal stem cells as cellular vectors for pediatric neurological disorders

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