Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats. (4th December 2019)

• Record Type: Journal Article
• Authors: Marsala, Martin; Kamizato, Kota; Tadokoro, Takahiro; Navarro, Michael; Juhas, Stefan; Juhasova, Jana; Marsala, Silvia; Studenovska, Hana; Proks, Vladimir; Hazel, Tom; Johe, Karl; Kakinohana, Manabu; Driscoll, Shawn; Glenn, Thomas; Pfaff, Samuel; Ciacci, Joseph
• Is Part Of: Stem cells translational medicine. Volume 9:Number 2(2020)
• Page Start: 177
• Page End: 188
• Publication Date: 2019-12-04
• Subjects: glia limitans formation from grafted neural precursors -- human-specific mRNA sequencing -- immunodeficient rat -- neuraxial neural precursor migration -- subpial stem cell injection; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.19-0156
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Neural precursor cells (NSCs) hold great potential to treat a variety of neurodegenerative diseases and injuries to the spinal cord. However, current delivery techniques require an invasive approach in which an injection needle is advanced into the spinal parenchyma to deliver cells of interest. As such, this approach is associated with an inherent risk of spinal injury, as well as a limited delivery of cells into multiple spinal segments. Here, we characterize the use of a novel cell delivery technique that employs single bolus cell injections into the spinal subpial space. In immunodeficient rats, two subpial injections of human NSCs were performed in the cervical and lumbar spinal cord, respectively. The survival, distribution, and phenotype of transplanted cells were assessed 6-8 months after injection. Immunofluorescence staining and mRNA sequencing analysis demonstrated a near-complete occupation of the spinal cord by injected cells, in which transplanted human NSCs (hNSCs) preferentially acquired glial phenotypes, expressing oligodendrocyte (Olig2, APC) or astrocyte (GFAP) markers. In the outermost layer of the spinal cord, injected hNSCs differentiated into glia limitans-forming astrocytes and expressed human-specific superoxide dismutase and laminin. All animals showed normal neurological function for the duration of the analysis. These data show that the subpial cell delivery technique is highly effective in populating the entire spinal cord with injected NSCs, and has a potential for clinical use in cell replacement therapies for the treatment of ALS, multiple sclerosis, or spinal cord injury. : Abstract : Migration and functional maturation of subpially injected human neural precursor cells (hNSCs) in immunodeficient rats: after injection, cells migrate into the spinal parenchyma across the glia limitans. A subpopulation of cells differentiate into astrocytes, incorporate into glia limitans and express functional markers characteristic if glia limitans-forming astrocytes, including superoxide dismutase (SOD) and laminin. The other population of injected cells continues to migrate into the spinal parenchyma.