Grafted human induced pluripotent stem cells improve the outcome of spinal cord injury: modulation of the lesion microenvironment

Sci Rep. 2020 Dec 29;10(1):22414. doi: 10.1038/s41598-020-79846-2.

Abstract

Spinal cord injury results in irreversible tissue damage followed by a very limited recovery of function. In this study we investigated whether transplantation of undifferentiated human induced pluripotent stem cells (hiPSCs) into the injured rat spinal cord is able to induce morphological and functional improvement. hiPSCs were grafted intraspinally or intravenously one week after a thoracic (T11) spinal cord contusion injury performed in Fischer 344 rats. Grafted animals showed significantly better functional recovery than the control rats which received only contusion injury. Morphologically, the contusion cavity was significantly smaller, and the amount of spared tissue was significantly greater in grafted animals than in controls. Retrograde tracing studies showed a statistically significant increase in the number of FB-labeled neurons in different segments of the spinal cord, the brainstem and the sensorimotor cortex. The extent of functional improvement was inversely related to the amount of chondroitin-sulphate around the cavity and the astrocytic and microglial reactions in the injured segment. The grafts produced GDNF, IL-10 and MIP1-alpha for at least one week. These data suggest that grafted undifferentiated hiPSCs are able to induce morphological and functional recovery after spinal cord contusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL3 / metabolism
  • Disease Models, Animal
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / pathology
  • Induced Pluripotent Stem Cells / transplantation
  • Interleukin-10 / metabolism
  • Rats
  • Rats, Inbred F344
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology
  • Spinal Cord Injuries* / therapy
  • Stem Cell Niche*
  • Stem Cell Transplantation*

Substances

  • CCL3 protein, human
  • Chemokine CCL3
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • IL10 protein, human
  • Interleukin-10