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Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats

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Abstract

Mesenchymal stem cells have been intensively studied for their potential use in reparative strategies for neurodegenerative diseases and traumatic injuries. We used mesenchymal stem cells (rMSC) from rat bone marrow to evaluate the therapeutic potential after spinal cord injury (SCI). Immunohistochemistry confirmed a large number of apoptotic neurons and oligodendrocytes in caudal segments 2 mm away from the lesion site. Expression of caspase-3 on both neurons and oligodendrocytes after SCI was significantly downregulated by rMSC. Caspase-3 downregulation by rMSC involves increased expression of FLIP and XIAP in the cytosol and inhibition of PARP cleavage in the nucleus. Animals treated with rMSC had higher Basso, Beattie, Bresnahan (BBB) locomotor scoring and better recovery of hind limb sensitivity. Treatment with rMSC had a positive effect on behavioral outcome and histopathological assessment after SCI. The ability of rMSC to incorporate into the spinal cord, differentiate and to improve locomotor recovery hold promise for a potential cure after SCI.

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Abbreviations

APC:

Adenomatous polyposis coli

BBB:

Basso Beattie Bresnahan locomotor scoring

BCA:

Bicinchoninic acid

BDNF:

Brain derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

BSA:

Bovine serum albumin

CHAPS:

3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate

CNPase:

2′,3′-cyclicnucleotide-3′-phosphodiesterase

DAB:

Diaminobenzidine

DAPI :

4′,6-Diamidino-2-phenylindole dihydrochloride

DPI:

Days post injury

DTT:

Dithiothreitol

FBS:

Fetal bovine serum

FITC:

Fluorescein isothiocyanate

FLIP:

FLICE-inhibitory protein

GFAP:

Glial fibrillary acidic protein

hEGF:

Human epidermal growth factor

HRP:

Horseradish peroxidase

β-NGF:

Beta-nerve growth factor

NF-200:

Neurofilament H-200 kD

NT-3:

Neurotrophic hormone-3

PARP:

Poly[ADP-ribose] polymerase

PBS:

Phosphate buffered saline

PMSF:

Phenyl methane sulfonyl fluoride

RA:

Retinoic acid

rMSC:

Rat bone marrow mesenchymal stem cells

SCI:

Spinal cord injury

XIAP:

X-linked inhibitor of apoptosis protein

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Acknowledgments

We thank Noorjehan Ali for technical assistance. We thank Shellee Abraham for manuscript preparation and Diana Meister and Sushma Jasti for manuscript review. This research was supported by National Cancer Institute Grant CA 75557, CA 92393, CA 95058, CA 116708, N.I.N.D.S. NS47699 and NS57529, and Caterpillar, Inc., OSF Saint Francis, Inc., Peoria, IL (to J.S.R.).

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Authors and Affiliations

  1. Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL, 61656, USA

    Venkata Ramesh Dasari & Jasti S. Rao

  2. Department of Neurosurgery, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL, 61656, USA

    Daniel G. Spomar, Jasti S. Rao & Dzung H. Dinh

  3. Department of Biology, Bradley University, Peoria, IL, 61625, USA

    Craig Cady

  4. Department of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL, 61656, USA

    Meena Gujrati

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  1. Venkata Ramesh Dasari
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Correspondence to Dzung H. Dinh.

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Special issue in honor of Naren Banik.

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Dasari, V.R., Spomar, D.G., Cady, C. et al. Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats. Neurochem Res 32, 2080–2093 (2007). https://doi.org/10.1007/s11064-007-9368-z

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  • DOI: https://doi.org/10.1007/s11064-007-9368-z

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