Open AccessActivated Spinal Cord Ependymal Stem Cells Rescue Neurological Function
Author(s) -
MorenoManzano Victoria,
RodríguezJiménez Francisco Javier,
GarcíaRoselló Mireia,
Laínez Sergio,
Erceg Slaven,
Calvo Maria Teresa,
Ronaghi Mohammad,
Lloret Maria,
PlanellsCases Rosa,
SánchezPuelles Jose María,
Stojkovic Miodrag
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.24
Subject(s) - biology , spinal cord injury , stem cell , ependymal cell , progenitor cell , neural stem cell , spinal cord , transplantation , neurosphere , microbiology and biotechnology , neuroscience , adult stem cell , cellular differentiation , medicine , biochemistry , gene
Spinal cord injury (SCI) is a major cause of paralysis. Currently, there are no effective therapies to reverse this disabling condition. The presence of ependymal stem/progenitor cells (epSPCs) in the adult spinal cord suggests that endogenous stem cell‐associated mechanisms might be exploited to repair spinal cord lesions. epSPC cells that proliferate after SCI are recruited by the injured zone, and can be modulated by innate and adaptive immune responses. Here we demonstrate that when epSPCs are cultured from rats with a SCI (ependymal stem/progenitor cells injury [epSPCi]), these cells proliferate 10 times faster in vitro than epSPC derived from control animals and display enhanced self renewal. Genetic profile analysis revealed an important influence of inflammation on signaling pathways in epSPCi after injury, including the upregulation of Jak/Stat and mitogen activated protein kinase pathways. Although neurospheres derived from either epSPCs or epSPCi differentiated efficiently to oligodendrocites and functional spinal motoneurons, a better yield of differentiated cells was consistently obtained from epSPCi cultures. Acute transplantation of undifferentiated epSPCi or the resulting oligodendrocyte precursor cells into a rat model of severe spinal cord contusion produced a significant recovery of motor activity 1 week after injury. These transplanted cells migrated long distances from the rostral and caudal regions of the transplant to the neurofilament‐labeled axons in and around the lesion zone. Our findings demonstrate that modulation of endogenous epSPCs represents a viable cell‐based strategy for restoring neuronal dysfunction in patients with spinal cord damage. S TEM C ELLS 2009;27:733–743