Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model

J Neurosci Res. 2015 Dec;93(12):1826-38. doi: 10.1002/jnr.23636. Epub 2015 Aug 24.

Abstract

Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine.

Keywords: biomaterial; microfiber; neural stem/progenitor cell; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biocompatible Materials / therapeutic use
  • Cell Differentiation
  • Cells, Cultured
  • Disease Models, Animal
  • Embryo, Mammalian
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Motor Activity / physiology
  • Nerve Fibers / physiology*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation
  • Recovery of Function
  • Spinal Cord Diseases / mortality*
  • Spinal Cord Diseases / surgery*
  • Stem Cell Transplantation / methods*
  • Time Factors

Substances

  • Biocompatible Materials
  • Nerve Tissue Proteins
  • Green Fluorescent Proteins