Preconditioning and Cellular Engineering to Increase the Survival of Transplanted Neural Stem Cells for Motor Neuron Disease Therapy

Abstract

Despite the extensive research effort that has been made in the field, motor neuron diseases, namely, amyotrophic lateral sclerosis and spinal muscular atrophies, still represent an overwhelming cause of morbidity and mortality worldwide. Exogenous neural stem cell-based transplantation approaches have been investigated as multifaceted strategies to both protect and repair upper and lower motor neurons from degeneration and inflammation. Transplanted neural stem cells (NSCs) exert their beneficial effects not only through the replacement of damaged cells but also via bystander immunomodulatory and neurotrophic actions. Notwithstanding these promising findings, the clinical translatability of such techniques is jeopardized by the limited engraftment success and survival of transplanted cells within the hostile disease microenvironment. To overcome this obstacle, different methods to enhance graft survival, stability, and therapeutic potential have been developed, including environmental stress preconditioning, biopolymers scaffolds, and genetic engineering. In this review, we discuss current engineering techniques aimed at the exploitation of the migratory, proliferative, and secretive capacity of NSCs and their relevance for the therapeutic arsenal against motor neuron disorders and other neurological disorders.

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Fig. 1

Abbreviations

ALS:

amyotrophic lateral sclerosis

BDNF:

brain-derived neurotrophic factor

CNS:

central nervous system

GDNF:

glial-derived neurotrophic factor

HMGB1:

high-mobility group box 1

IPSC:

induced pluripotent stem cell

MHC:

major histocompatibility complex

MND:

motor neuron disorder

NGF:

nerve growth factor

NPC:

neural progenitor cell

NSC:

neural stem cell

SMA:

spinal muscular atrophy

SMARD1:

spinal muscular atrophy with respiratory distress type 1

VEGF:

vascular endothelial growth facto

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Acknowledgments

The following grant support is gratefully acknowledged: Italian Ministry of Health–RF-2016-02362317 and AFM-Telethon-2015, “Optimized Transplantation of hiPSC-derived LeX+CXCR4+VLA4 neural stem cells as a therapy for SMARD1” to GPC, and FP7-PEOPLE-2013-IRSES no. 612578 to SC. We thank the Associazione Amici del Centro Dino Ferrari for its support.

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Correspondence to Stefania Corti.

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Abati, E., Bresolin, N., Comi, G.P. et al. Preconditioning and Cellular Engineering to Increase the Survival of Transplanted Neural Stem Cells for Motor Neuron Disease Therapy. Mol Neurobiol 56, 3356–3367 (2019). https://doi.org/10.1007/s12035-018-1305-4

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Keywords

  • Stem cell transplantation
  • Stem cells
  • Neural stem cells
  • Cellular engineering
  • Preconditioning
  • Motor neuron diseases
  • Amyotrophic lateral sclerosis
  • Spinal muscular atrophy