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Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing
- Source :
- Stem Cells Translational Medicine
- Publication Year :
- 2018
- Publisher :
- John Wiley & Sons, Inc., 2018.
-
Abstract
- Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency. The oNPCs derived from different lines of human NPCs showed similar characteristics in vitro. To assess the in vivo efficacy of this approach, we used oNPCs derived from drNPCs and transplanted them into a SCI model in immunodeficient Rowett Nude (RNU) rats. The transplanted cells showed significant migration along the rostrocaudal axis and proportionally greater differentiation into oligodendrocytes. These cells promoted perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor function. Moreover, after transplantation of the oNPCs into intact spinal cords of immunodeficient NOD/SCID mice, we detected no evidence of tumor formation even after 5 months of observation. Thus, biasing drNPC differentiation along an oligodendroglial lineage represents a promising approach to promote tissue sparing, axonal remyelination, and neural repair after traumatic SCI.
- Subjects :
- 0301 basic medicine
Transplantation, Heterologous
Nod
Stem cells
Spinal cord injury
Mice, SCID
Biology
03 medical and health sciences
Mice
Rats, Nude
0302 clinical medicine
Translational Research Articles and Reviews
Neural Stem Cells
Mice, Inbred NOD
Precursor cell
medicine
Regeneration
Animals
Humans
Cell Lineage
Remyelination
Spinal Cord Injuries
Neurons
Oligodendrocytes
Regeneration (biology)
Cell Differentiation
Cell Biology
General Medicine
Recovery of Function
medicine.disease
Neural stem cell
Axons
Cell biology
Rats
Transplantation
Disease Models, Animal
Oligodendroglia
030104 developmental biology
medicine.anatomical_structure
Oligodendrogenic neural progenitor cells
Spinal Cord
Female
Stem cell
030217 neurology & neurosurgery
Developmental Biology
Tissue‐Specific Progenitor and Stem Cells
Subjects
Details
- Language :
- English
- ISSN :
- 21576580 and 21576564
- Volume :
- 7
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Stem Cells Translational Medicine
- Accession number :
- edsair.doi.dedup.....0d612ea27d1870633a888760504d35c1