title: Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres.
abstract: Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.
authors.affiliation: Department of Neuroscience, Neuroanatomy, Uppsala University Biomedical Center, Uppsala, Sweden.
authors.forename: Niclas
authors.initials: N
authors.lastname: König
authors.forename: Elisabet
authors.initials: E
authors.lastname: Åkesson
authors.forename: Michèle
authors.initials: M
authors.lastname: Telorack
authors.forename: Svitlana
authors.initials: S
authors.lastname: Vasylovska
authors.forename: Anongnad
authors.initials: A
authors.lastname: Ngamjariyawat
authors.forename: Erik
authors.initials: E
authors.lastname: Sundström
authors.forename: Andreas
authors.initials: A
authors.lastname: Oster
authors.forename: Carl
authors.initials: C
authors.lastname: Trolle
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
authors.forename: Håkan
authors.initials: H
authors.lastname: Aldskogius
authors.forename: Åke
authors.initials: Å
authors.lastname: Seiger
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kozlova
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000637:transplantation*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D011994:Recombinant Proteins; C493464:SLC17A7 protein, human; D050598:Vesicular Glutamate Transport Protein 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase