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

  • Elena Abati
  • Nereo Bresolin
  • Giacomo Pietro Comi
  • Stefania CortiEmail author
Article

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.

Keywords

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

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

Notes

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), Neuroscience SectionUniversity of MilanMilanItaly
  2. 2.Neurology UnitFoundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly

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