Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats
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 inte...
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Online Access: | https://doi.org/10.1002/sctm.19-0156 |
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doaj-ff2e2f3f002c42e4b2b8ed1b25389c952020-11-25T02:18:27ZengWileyStem Cells Translational Medicine2157-65642157-65802020-02-019217718810.1002/sctm.19-0156Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient ratsMartin Marsala0Kota Kamizato1Takahiro Tadokoro2Michael Navarro3Stefan Juhas4Jana Juhasova5Silvia Marsala6Hana Studenovska7Vladimir Proks8Tom Hazel9Karl Johe10Manabu Kakinohana11Shawn Driscoll12Thomas Glenn13Samuel Pfaff14Joseph Ciacci15Neuroregeneration Laboratory, Department of Anesthesiology University of California, San Diego La Jolla CaliforniaNeuroregeneration Laboratory, Department of Anesthesiology University of California, San Diego La Jolla CaliforniaNeuroregeneration Laboratory, Department of Anesthesiology University of California, San Diego La Jolla CaliforniaNeuroregeneration Laboratory, Department of Anesthesiology University of California, San Diego La Jolla CaliforniaInstitute of Animal Physiology and Genetics, Czech Academy of Sciences Libechov Czech RepublicInstitute of Animal Physiology and Genetics, Czech Academy of Sciences Libechov Czech RepublicNeuroregeneration Laboratory, Department of Anesthesiology University of California, San Diego La Jolla CaliforniaDepartment of Biomaterials and Bioanalogous Systems Institute of Macromolecular Chemistry, Czech Academy of Sciences Prague Czech RepublicDepartment of Biomaterials and Bioanalogous Systems Institute of Macromolecular Chemistry, Czech Academy of Sciences Prague Czech RepublicNeuralstem Inc. Germantown MarylandNeuralstem Inc. Germantown MarylandDepartment of Anesthesia University of Ryukyus Okinawa JapanGene Expression Laboratory Howard Hughes Medical Institute, Salk Institute for Biological Studies La Jolla CaliforniaGene Expression Laboratory Howard Hughes Medical Institute, Salk Institute for Biological Studies La Jolla CaliforniaGene Expression Laboratory Howard Hughes Medical Institute, Salk Institute for Biological Studies La Jolla CaliforniaDepartment of Neurosurgery University of California, San Diego La Jolla CaliforniaAbstract 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.https://doi.org/10.1002/sctm.19-0156glia limitans formation from grafted neural precursorshuman‐specific mRNA sequencingimmunodeficient ratneuraxial neural precursor migrationsubpial stem cell injection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martin Marsala Kota Kamizato Takahiro Tadokoro Michael Navarro Stefan Juhas Jana Juhasova Silvia Marsala Hana Studenovska Vladimir Proks Tom Hazel Karl Johe Manabu Kakinohana Shawn Driscoll Thomas Glenn Samuel Pfaff Joseph Ciacci |
spellingShingle |
Martin Marsala Kota Kamizato Takahiro Tadokoro Michael Navarro Stefan Juhas Jana Juhasova Silvia Marsala Hana Studenovska Vladimir Proks Tom Hazel Karl Johe Manabu Kakinohana Shawn Driscoll Thomas Glenn Samuel Pfaff Joseph Ciacci Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats Stem Cells Translational Medicine glia limitans formation from grafted neural precursors human‐specific mRNA sequencing immunodeficient rat neuraxial neural precursor migration subpial stem cell injection |
author_facet |
Martin Marsala Kota Kamizato Takahiro Tadokoro Michael Navarro Stefan Juhas Jana Juhasova Silvia Marsala Hana Studenovska Vladimir Proks Tom Hazel Karl Johe Manabu Kakinohana Shawn Driscoll Thomas Glenn Samuel Pfaff Joseph Ciacci |
author_sort |
Martin Marsala |
title |
Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
title_short |
Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
title_full |
Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
title_fullStr |
Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
title_full_unstemmed |
Spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
title_sort |
spinal parenchymal occupation by neural stem cells after subpial delivery in adult immunodeficient rats |
publisher |
Wiley |
series |
Stem Cells Translational Medicine |
issn |
2157-6564 2157-6580 |
publishDate |
2020-02-01 |
description |
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. |
topic |
glia limitans formation from grafted neural precursors human‐specific mRNA sequencing immunodeficient rat neuraxial neural precursor migration subpial stem cell injection |
url |
https://doi.org/10.1002/sctm.19-0156 |
work_keys_str_mv |
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1724882009030918144 |