Abstract
Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Stem Cells 2011;29:2062–2076.
Highlights
Neural stem/precursor cells (NSCs) are hosted in niches and can be activated following injuries and other neurologic degenerative disorders [1,2,3,4] as well as during learning [5] and pharmacological treatments [6]
To determine the proliferation rate, cells were loaded with carboxyfluorescein succinimidyl ester and 5 days later, staining dilution was determined by fluorescence-activated cell sorting (FACS) analysis
After 1 month in culture, neurospheres derived from meningeal tissue extracts were composed of a mixture of nestin-positive cells that were either neural lineage negative or neural differentiated cells expressing microtubule-associated protein 2 (MAP2) or glial fibrillary acidic protein (GFAP; Fig. 1C)
Summary
Neural stem/precursor cells (NSCs) are hosted in niches and can be activated following injuries and other neurologic degenerative disorders [1,2,3,4] as well as during learning [5] and pharmacological treatments [6]. The retina [11] and the central canal of the spinal cord (SC) were shown to host NSC [12]. Despite their properties of self-renewal and neuroglial differentiation, the use of NSC in regenerative medicine is still limited mainly because these cells are located in distinct, small, and hardly accessible areas of the CNS [13]. Defining the functional significance of meninges, their involvement in neurological disorders and strategies for their exploitation as NSC sources could prove a strategic turnaround in regenerative therapeutics of the CNS
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