Elsevier

Experimental Neurology

Volume 137, Issue 2, February 1996, Pages 376-388
Experimental Neurology

Regular Article
Survival and Differentiation of Rat and Human Epidermal Growth Factor-Responsive Precursor Cells Following Grafting into the Lesioned Adult Central Nervous System

https://doi.org/10.1006/exnr.1996.0039Get rights and content

Abstract

Epidermal Growth Factor (EGF)-responsive stem cells isolated from the developing central nervous system (CNS) can be expanded exponentially in culture while retaining the ability to differentiate into neurons and glia. As such, they represent a possible source of tissue for neural transplantation, providing they can survive and mature following grafting into the adult brain. In this study we have shown that purified rat stem cells generated from either the embryonic mesencephalon or the striatum can survive grafting into the striatum of rats with either ibotenic acid or nigrostriatal dopamine lesions. However, transplanted stem cells do not survive as a large mass typical of primary embryonic CNS tissue grafts, but in contrast form thin grafts containing only a small number of surviving cells. There was no extensive migration of transplanted stem cells labeled with either thelac-zgene or bromodeoxyuridine into the host region surrounding the graft, although a small number of labeled cells were seen in the ventral striatum some distance from the site of implantation. Some of these appeared to differentiate into dopamine neurons, particularly when the developing mesencephalon was used as the starting material for generating the stem cells. EGF-responsive stem cells could also be isolated from the mesencephalon of developing human embryos and expanded in culture, but only grew in large numbers when the gestational age of the embryo was greater than 11 weeks. Purified human CNS stem cells were also transplanted into immunosuppressed rats with nigrostriatal lesions and formed thin grafts similar to those seen when using rat stem cells. However, when primary cultures of human mesencephalon were grown with EGF for only 10 days and this mixture of stem cells and primary neural tissue was transplanted into the dopamine-depleted striatum, large well-formed grafts developed. These contained mostly small undifferentiated cells intermixed with a number of well-differentiated TH-positive neurons. These results show that purified populations of rat or human EGF-responsive CNS stem cells do not form large graft masses or migrate extensively into the surrounding host tissues when transplanted into the adult striatum. However, modifications of the growth conditionsin vitromay lead to an improvement of their survivalin vivo.

References (0)

Cited by (281)

  • Strategies for bringing stem cell-derived dopamine neurons to the clinic—The NYSTEM trial

    2017, Progress in Brain Research
    Citation Excerpt :

    The most likely initial choice for those efforts was NSCs with pluripotent stem cells serving as an interesting alternative. Extensive studies using NSCs or neural precursor cell (NPC) populations revealed that most available sources yield engraftable DA neurons at very low efficiencies (Ourednik et al., 2002; Svendsen et al., 1996). The reason for their limited differentiation potential is due to the highly specific progenitor population present in the midbrain that give rise to mDA neurons during mouse and human development, with unique gene expression profiles and lineage potential, as detailed in a very elegant, recent single cells transcriptome study (La Manno et al., 2016).

View all citing articles on Scopus
1

To whom correspondence should be addressed.

View full text