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1.
Sci Rep ; 11(1): 16673, 2021 08 17.
Article in English | MEDLINE | ID: mdl-34404826

ABSTRACT

This study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years' follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.


Subject(s)
Lumbar Vertebrae/surgery , Spondylolisthesis/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Period , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome
2.
Neuropathology ; 31(1): 48-58, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20573032

ABSTRACT

The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell-derived Schwann cells (hBMSC-SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC-SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC-SC were detected using cytokine antibody array. Immunosuppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC-SC (hBMSC-SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl-violet staining revealed that the area of cystic cavity was smaller in the hBMSC-SC group than that in the control group. Immunohistochemistry revealed that the number of anti-growth-associated protein-43-positive nerve fibers was significantly larger in the hBMSC-SC group than that in the control group. At the same time, the number of tyrosine hydroxylase- or serotonin-positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC-SC group than that in the control group. In electron microscopy, formation of peripheral-type myelin was recognized near the lesion epicenter in the hBMSC-SC group. Hind limb function recovered significantly in the hBMSC-SC group compared with the control group. In conclusion, the functions of hBMSC-SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury.


Subject(s)
Recovery of Function , Schwann Cells/transplantation , Spinal Cord Injuries/pathology , Spinal Cord Injuries/surgery , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Marrow Transplantation , Cell Differentiation , Cysts/pathology , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron, Transmission , Nerve Regeneration/physiology , Rats , Rats, Wistar , Schwann Cells/metabolism , Schwann Cells/ultrastructure , Spinal Cord Injuries/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Stromal Cells/cytology , Stromal Cells/metabolism , Young Adult
3.
Acta Neuropathol ; 117(3): 321-8, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19125256

ABSTRACT

Macrophage migration inhibitory factor (MIF) is a multipotential protein that acts as a proinflammatory cytokine, a pituitary hormone, and a cell proliferation and migration factor. The objective of this study was to elucidate the role of MIF in spinal cord injury (SCI) using female MIF knockout (KO) mice. Mouse spinal cord compression injury was produced by application of a static load (T8 level, 20 g, 5 min). We analyzed the motor function of the hind limbs and performed histological examinations. Hind-limb function recovered significantly in the KO mice starting from three weeks after injury. Cresyl-violet staining revealed that the number of surviving neurons in the KO mice was significantly larger than that of WT mice six weeks after injury. Immunohistochemical analysis revealed that the number of NeuN/caspase-3-active, double-positive, apoptotic neurons in the KO mice was significantly smaller than that of the WT mice 24 and 72 h after SCI. These results were related to in-vitro studies showing increased resistance of cerebellar granular neurons from MIF-KO animals to glutamate neurotoxicity. These results suggest that MIF existence hinders neuronal survival after SCI. Suppression of MIF may attenuate detrimental secondary molecular responses of the injured spinal cord.


Subject(s)
Cell Death , Locomotion , Macrophage Migration-Inhibitory Factors/deficiency , Neurons/metabolism , Recovery of Function , Spinal Cord Injuries , Analysis of Variance , Animals , Caspase 3/metabolism , Cells, Cultured , Cerebellum/pathology , DNA-Binding Proteins , Extremities/physiopathology , Female , Glutamic Acid/toxicity , Immunohistochemistry , Macrophage Migration-Inhibitory Factors/genetics , Mice , Mice, Inbred BALB C , Mice, Knockout , Nerve Tissue Proteins/metabolism , Neurons/pathology , Nuclear Proteins/metabolism , Spinal Cord Compression/complications , Spinal Cord Injuries/etiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Time Factors
4.
J Neurosurg Spine ; 9(6): 600-10, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19035756

ABSTRACT

OBJECT: The authors previously reported that Schwann cells (SCs) could be derived from bone marrow stromal cells (BMSCs) in vitro and that they promoted axonal regeneration of completely transected rat spinal cords in vivo. The aim of the present study is to evaluate the efficacy of transplanted BMSC-derived SCs (BMSC-SCs) in a rat model of spinal cord contusion, which is relevant to clinical spinal cord injury. METHODS: Bone marrow stromal cells were cultured as plastic-adherent cells from the bone marrow of GFPtransgenic rats. The BMSC-SCs were derived from BMSCs in vitro with sequential treatment using beta-mercaptoethanol, all-trans-retinoic acid, forskolin, basic fibroblast growth factor, platelet derived-growth factor, and heregulin. Schwann cells were cultured from the sciatic nerve of neonatal, GFP-transgenic rats. Immunocytochemical analysis and the reverse transcriptase-polymerase chain reaction were performed to characterize the BMSC-SCs. For transplantation, contusions with the New York University impactor were delivered at T-9 in 10- to 11-week-old male Wistar rats. Four groups of rats received injections at the injury site 7 days postinjury: the first received BMSCSCs and matrigel, a second received peripheral SCs and matrigel, a third group received BMSCs and matrigel, and a fourth group received matrigel alone. Histological and immunohistochemical studies, electron microscopy, and functional assessments were performed to evaluate the therapeutic effects of BMSC-SC transplantation. RESULTS: Immunohistochemical analysis and reverse transcriptase-polymerase chain reaction revealed that BMSC-SCs have characteristics similar to SCs not only in their morphological characteristics but also in their immunocytochemical phenotype and genotype. Histological examination revealed that the area of the cystic cavity was significantly reduced in the BMSC-SC and SC groups compared with the control rats. Immunohistochemical analysis showed that transplanted BMSCs, BMSC-SCs, and SCs all maintained their original phenotypes. The BMSC-SC and SC groups had a larger number of tyrosine hydroxilase-positive fibers than the control group, and the BMSC-SC group had more serotonin-positive fibers than the BMSC or control group. The BMSC-SC group showed significantly better hindlimb functional recovery than in the BMSC and control group. Electron microscopy revealed that transplanted BMSC-SCs existed in association with the host axons. CONCLUSIONS: Based on their findings, the authors concluded that BMSC-SC transplantation reduces the size of the cystic cavity, promotes axonal regeneration and sparing, results in hindlimb functional recovery, and can be a useful tool for spinal cord injury as a substitute for SCs.


Subject(s)
Axons/physiology , Bone Marrow Transplantation/methods , Nerve Regeneration , Schwann Cells , Spinal Cord Injuries/therapy , Stromal Cells/cytology , Animals , Cell Differentiation , Male , Rats , Rats, Wistar , Recovery of Function , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Thoracic Vertebrae
5.
J Neuropathol Exp Neurol ; 66(8): 724-31, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17882016

ABSTRACT

Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immunohistochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.


Subject(s)
Granulocyte Colony-Stimulating Factor/therapeutic use , Neurons/drug effects , Recovery of Function/drug effects , Spinal Cord Injuries , Animals , Animals, Newborn , Behavior, Animal , Caspase 3/metabolism , Cell Death/drug effects , Cells, Cultured , Cerebellum/cytology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Mice , Mice, Inbred BALB C , Neurons/physiology , Phosphopyruvate Hydratase/metabolism , RNA, Messenger/metabolism , Receptors, Granulocyte Colony-Stimulating Factor/genetics , Receptors, Granulocyte Colony-Stimulating Factor/metabolism , Reverse Transcriptase Polymerase Chain Reaction/methods , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Statistics, Nonparametric , Time Factors
6.
Eur Spine J ; 16(12): 2206-14, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17885772

ABSTRACT

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying beta-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury.


Subject(s)
Bone Marrow Transplantation/methods , Brain-Derived Neurotrophic Factor/genetics , Gene Transfer Techniques , Spinal Cord Injuries/therapy , Stromal Cells/transplantation , Adenoviridae/genetics , Animals , Bone Marrow Cells/metabolism , Bone Marrow Cells/virology , Cells, Cultured , Disease Models, Animal , Genetic Vectors/genetics , Growth Cones/metabolism , Growth Cones/ultrastructure , Male , Nerve Regeneration/genetics , Neuronal Plasticity/genetics , Rats , Rats, Wistar , Recovery of Function/genetics , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology , Stromal Cells/metabolism , Stromal Cells/virology , Treatment Outcome
7.
Brain Res ; 1149: 223-31, 2007 May 29.
Article in English | MEDLINE | ID: mdl-17391650

ABSTRACT

The aim of the present study was to elucidate the effects of granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of bone marrow-derived stem cells on the injured spinal cord. Bone marrow cells of green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated C57BL/6 mice. Four weeks after bone marrow transplantation, spinal cord injury was produced by a static load (20 g, 5 min) at T8 level. G-CSF (200 microg/kg/day) was injected subcutaneously for 5 days. Immunohistochemistry for GFP and cell lineage markers was performed to evaluate G-CSF-mediated mobilization of bone marrow-derived cells into injured spinal cord. Hind limb locomotor recovery was assessed for 6 weeks. Immunohistochemistry revealed that G-CSF increased the number of GFP-positive cells in injured spinal cord, indicating that bone marrow-derived cells were mobilized and migrated into injured spinal cord. The numbers of double positive cells for GFP and glial markers were larger in the G-CSF treated mice than in the control mice. Luxol Fast Blue staining revealed that G-CSF promoted white matter sparing. G-CSF treated mice showed significant recovery of hind limb function compared to that of the control mice. In conclusion, G-CSF showed efficacy for spinal cord injury treatment through mobilization of bone marrow-derived cells.


Subject(s)
Bone Marrow Cells/metabolism , Bone Marrow Transplantation , Granulocyte Colony-Stimulating Factor/therapeutic use , Nerve Regeneration/physiology , Recovery of Function/physiology , Spinal Cord Injuries/therapy , Animals , Cell Movement/physiology , Granulocyte Colony-Stimulating Factor/metabolism , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Spinal Cord Compression/therapy
8.
J Neurosurg Spine ; 5(5): 424-33, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17120892

ABSTRACT

OBJECT: The use of human umbilical cord blood (HUCB) cells has been reported to improve functional recovery in cases of central nervous system injuries such as stroke, traumatic brain injury, and spinal cord injury (SCI). The authors investigated the effects of hemopoietic stem cells that were derived from HUCB and transplanted into the injured spinal cords of rats. METHODS: One week after injury, an HUCB fraction enriched in CD34-positive cells was transplanted into the experimental group. In control animals, vehicle (Matrigel) was transplanted. Recovery of motor functions was assessed using the Basso-Beattie-Bresnahan Locomotor Scale, and immunohistochemical examinations were performed. Cells from HUCB that were CD34 positive improved functional recovery, reduced the area of the cystic cavity at the site of injury, increased the volume of residual white matter, and promoted the regeneration or sparing of axons in the injured spinal cord. Immunohistochemical examination revealed that transplanted CD34-positive cells survived in the host spinal cord for at least 3 weeks after transplantation but had disappeared by 5 weeks. The transplanted cells were not positive for neural markers, but they were positive for hemopoietic markers. There was no evidence of an immune reaction at the site of injury in either group. CONCLUSIONS: These results suggest that transplantation of a CD34-positive fraction from HUCB may have therapeutic effects for SCI. The results of this study provide important preclinical data regarding HUCB stem cell-based therapy for SCI.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Spinal Cord Injuries/therapy , Transplantation, Heterologous , Animals , Antigens, CD34/physiology , Disease Models, Animal , Hindlimb/physiopathology , Humans , Infant, Newborn , Male , Rats , Rats, Wistar , Recovery of Function/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology
9.
Neuroreport ; 16(16): 1763-7, 2005 Nov 07.
Article in English | MEDLINE | ID: mdl-16237323

ABSTRACT

We compared the effects of hematopoietic stem cell and marrow stromal cell transplantation for spinal cord injury in mice. From green fluorescent protein transgenic mouse bone marrow, lineage-negative, c-kit- and Sca-1-positive cells were sorted as hematopoietic stem cells and plastic-adherent cells were cultured as marrow stromal cells. One week after injury, hematopoietic stem cells or marrow stromal cells were injected into the lesioned site. Functional recovery was assessed and immunohistochemistry was performed. In the hematopoietic stem cell group, a portion of green fluorescent protein-positive cells expressed glial marker. In the marrow stem cell group, a number of green fluorescent protein and fibronectin-double positive cells were observed. No significant difference was observed in the recovery between both groups. Both hematopoietic stem cells and marrow stromal cells have the potential to restore the injured spinal cord and to promote functional recovery.


Subject(s)
Bone Marrow Cells/physiology , Bone Marrow Transplantation/methods , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/physiology , Spinal Cord Injuries/surgery , Adenomatous Polyposis Coli Protein/metabolism , Animals , Disease Models, Animal , Female , Fibronectins/metabolism , Flow Cytometry/methods , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Immunohistochemistry/methods , Leukocyte Common Antigens/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Time Factors
10.
J Neuropathol Exp Neurol ; 64(1): 37-45, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15715083

ABSTRACT

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.


Subject(s)
Axons/transplantation , Bone Marrow Transplantation/methods , Nerve Regeneration/physiology , Recovery of Function/physiology , Schwann Cells/transplantation , Spinal Cord Injuries/physiopathology , Animals , Immunohistochemistry , Male , Motor Activity/physiology , Rats , Rats, Wistar , Schwann Cells/cytology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Stromal Cells/cytology , Stromal Cells/transplantation , Thoracic Vertebrae/innervation , Thoracic Vertebrae/surgery , Time Factors
11.
J Neurotrauma ; 21(3): 329-37, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15115607

ABSTRACT

Neurotrophins have been shown to promote axonal regeneration, but the techniques available for delivering neurotrophins have limited effectiveness. The aim of this study was to evaluate the effect of adenovirus vector mediated gene transfer of brain-derived neurotrophic factor (BDNF) on axonal regeneration after spinal cord injury. We prepared adenovirus vectors encoding either beta-galactosidase (AxCALacZ) or BDNF (AxCABDNF). AxCALacZ was used to assess infection levels of the adenovirus BDNF produced by AxCABDNF was detected by Western blotting and its bioactivity was confirmed by bioassay. As a model of spinal cord injury, the rat spinal cord was completely transected at the T8 level. Immediately after transection, the vectors were injected into both stumps of the spinal cord. Axonal regeneration after transection was assessed by retrograde and anterograde tracing. In AxCALacZ-injected rats, adenovirus-infected cells were observed not only at the injected site but also in brainstem nuclei, as shown by LacZ expression. After the injection of the retrograde tracer fluorogold (FG) distal portion to the transection, AxCABDNF-injected rats showed FG-labeled neurons in the red nucleus. The anterograde tracer biotinylated dextran amine (BDA) injected into the red nucleus was also found in regenerating rubrospinal fibers distal to the transection. These tracing experiments demonstrated the regeneration of descending axons. In addition, rats of the AxCABDNF group showed significant locomotor recovery of hindlimb function, which was completely abolished by re-transection. These results indicate that the recovery was caused by regeneration of rubrospinal axons, not by simple enhancement of the central pattern generator.


Subject(s)
Axons/physiology , Brain-Derived Neurotrophic Factor/physiology , Gene Transfer Techniques , Nerve Regeneration/physiology , Spinal Cord Injuries/therapy , Adenoviridae , Animals , Genetic Vectors/therapeutic use , Lac Operon/physiology , Male , Rats , Rats, Wistar , Recovery of Function/physiology , Spinal Cord Injuries/physiopathology
12.
Acta Neuropathol ; 108(1): 31-6, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15067555

ABSTRACT

Macrophage migration inhibitory factor (MIF) is a multipotential protein that acts as a pro-inflammatory cytokine, pituitary hormone, immunoregulator, and mitogen. To elucidate function of MIF in spinal cord injury, we examined expression of MIF after compression-induced spinal cord injury using Northern blot analysis, in situ hybridization and immunohistochemistry. The MIF mRNA was up-regulated in injured spinal cord, peaking 3 days after injury shown by Northern blot analysis. In situ hybridization revealed up-regulation of MIF in microglia accumulating in the lesion epicenter 3 days after injury and astrocytes around the cystic cavity 1 week after injury. Double staining showed co-localization of MIF and tomato lectin in the lesioned site, indicating that microglia accumulating to the lesion epicenter express MIF. The time course of MIF expression is different from that of previous reports about cytokine expression peaking at earlier time points; thus, it is unlikely that MIF acts as a pro-inflammatory factor in the present study. The MIF may contribute to proliferation of astrocytes around the lesioned site in spinal cord injury because of its cell proliferation-promoting property.


Subject(s)
Gene Expression Regulation/physiology , Macrophage Migration-Inhibitory Factors/metabolism , Spinal Cord Compression/metabolism , Spinal Cord Injuries/metabolism , Up-Regulation/physiology , Animals , Blotting, Northern/methods , Cell Count/methods , Immunohistochemistry/methods , In Situ Hybridization/methods , Macrophage Migration-Inhibitory Factors/genetics , Male , Microglia/metabolism , Plant Lectins/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction/methods , Spinal Cord Compression/complications , Spinal Cord Injuries/etiology , Time Factors
13.
J Neuropathol Exp Neurol ; 63(1): 64-72, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14748562

ABSTRACT

Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.


Subject(s)
Hematopoietic Stem Cell Transplantation , Recovery of Function , Spinal Cord Injuries/therapy , Animals , Astrocytes/cytology , Bone Marrow Cells/cytology , Cell Differentiation , Cell Lineage , Cell Survival , Disease Models, Animal , Female , Immunohistochemistry , In Situ Hybridization, Fluorescence , Mice , Neurons/cytology , Oligodendroglia/cytology
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