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Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications

Abstract

Axonal regeneration and formation of tripartite (axo-glial) junctions at damaged sites is a prerequisite for early repair of injured spinal cord. Transplantation of stem cells at such sites of damage which can generate both neuronal and glial population has gained impact in terms of recuperation upon infliction with spinal cord injury. In spite of the fact that a copious number of pre-clinical studies using different stem/progenitor cells have shown promising results at acute and subacute stages, at the chronic stages of injury their recovery rates have shown a drastic decline. Therefore, developing novel therapeutic strategies are the need of the hour in order to assuage secondary morbidity and effectuate improvement of the spinal cord injury (SCI)-afflicted patients’ quality of life. The present review aims at providing an overview of the current treatment strategies and also gives an insight into the potential cell-based therapies for the treatment of SCI.

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Fig. 1

Abbreviations

SCI:

Spinal cord injury

NSCISC:

National Spinal Cord Injury Statistical Center

GDP:

Gross domestic product

NSCT:

Neural stem cell transplantation

NSC:

Neural stem cell

ASIA:

American Spinal Cord Injury Association

TNFα:

Tumor necrosis factor alpha

IL-β:

Interleukin 1 beta

GFAP:

Glial fibrillary acidic protein

BBB:

Blood-brain barrier

GCV:

Ganciclovir

CSPGs:

Chondroitin sulfate proteoglycans

GAG:

Glycosaminoglycan

CNS:

Central nervous system

CNS:

Central nervous system

OPCs:

Oligodendrocyte progenitor cells

cABC:

Chondroitinase ABC

ATP:

Adenosine triphosphate

NO:

Nitric oxide

NADPH:

Nicotinamide adenine dinucleotide phosphate

ROS:

Reactive oxygen species

LPS:

Liposaccharides

MAG:

Myelin-associated glycoprotein

Omgp:

Oligodendrocyte myelin glycoprotein

MPSS:

Methylprednisolone

GK-11:

Gacyclidine

NTX:

N-terminal telopeptide

bALP:

Bone alkaline phosphatase

FIM:

Functional Independence Measure

COT:

Common Object Test

SVZ:

Subventricular zone

SGZ:

Subgranular zone

ESCs:

Embryonic stem cells

PSCs:

Pluripotent stem cells

NS/PCs:

Neural stem/progenitor cells

MSCs:

Mesenchymal stem cells

HSCs:

Hematopoietic stem cells

G-CSF:

Granulocyte colony-stimulating factor

HBO:

Hyperbaric oxygen

BSCB:

Blood-spinal cord barrier

NES:

Neuroepithelial stem cells

OECs:

Olfactory ensheathing cells

SCs:

Schwann cells

hGPCs:

Human glial progenitor cells

HGF:

Hepatocyte growth factor

BDNF:

Brain-derived neurotrophic factor

ECM:

Extracellular matrix

PGA:

Poly(glycolic acid)

PLA:

Poly(lactic acid)

BPA:

Blood pressure augmentation

BMMCs:

Bone marrow mononuclear cells

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Acknowledgements

The authors are thankful to Ms. Zera Mariyam for proofreading the manuscript.

Funding

Katari Venkatesh (KV) is supported by a National Post-Doctoral Fellowship (N-PDF) (File No: PDF/2016/003652/LS) from Science and Engineering Research Board (SERB), Department of Science and Technology, Govt. of India. Dwaipayan Sen (DS) is supported by a “Fast Track Young Scientist” grant (YSS/2014/000027) from the Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India. DS is also supported by a grant award from the Indian Council of Medical Research (ICMR), Sanction Order No. NCD/Ad-hoc/66/2016-17. The funding sources did not play any role in the research and/or preparation of the article, study design, data collection, analysis/interpretation of data, writing of the report, and decision to submit the article for publication.

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Venkatesh, K., Ghosh, S.K., Mullick, M. et al. Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications. Cell Tissue Res 377, 125–151 (2019). https://doi.org/10.1007/s00441-019-03039-1

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Keywords

  • Spinal cord injury
  • Neural stem cells
  • Biomaterial channels
  • Cell-matrix hybrids
  • Neuroregeneration
  • Remyelination