Physical exercise promotes integration of grafted cells and functional recovery in an acute stroke rat model

Stem Cell Reports. 2022 Feb 8;17(2):276-288. doi: 10.1016/j.stemcr.2021.12.006. Epub 2022 Jan 13.

Abstract

Human neural progenitor cell (hNPC) transplantation holds great potential to treat neurological diseases. However, hNPC grafts take a long time to differentiate into mature neurons due to their intrinsically prolonged developmental timetable. Here, we report that postoperative physical exercise (PE), a prevailing rehabilitation intervention, promotes the neuronal commitment, maturation, and integration of engrafted hNPCs, evidenced by forming more synapses, receiving more synaptic input from host neurons, and showing higher neuronal activity levels. More important, NPC transplantation, combined with PE, shows significant improvement in both structural and behavioral outcomes in stroke-damaged rats. PE enhances ingrowth of blood vessels around the infarction region and neural tract reorganization along the ischemic boundary. The combination of NPC transplantation and postoperative PE creates both a neurotrophic/growth factor-enriched proneuronal microenvironment and an ideal condition for activity-dependent plasticity to give full play to its effects. Our study provides a potential approach to treating patients with stroke injury.

Keywords: human neural progenitor cell; neuronal differentiation; physical exercise; stroke; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / physiology
  • Cellular Microenvironment
  • Disease Models, Animal
  • Humans
  • Male
  • Nerve Growth Factors / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation*
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Stroke / pathology
  • Stroke / therapy*
  • Synapses / metabolism
  • Transcriptome

Substances

  • Nerve Growth Factors