Substrate dependency of neurite outgrowth from adult human chromaffin cells. Inhibitory effects of human brain tissue.
Attempts to treat Parkinson's disease with grafts of chromaffin cells to the caudate nucleus have recently generated considerable interest. However, it is not known whether chromaffin cells can innervate the human central nervous system. We have directly addressed this question by measuring neurite outgrowth in cultures of normal adult human chromaffin cells on frozen sections of caudate nucleus and other substrates, a technique previously employed in animal studies. Chromaffin cells from radical nephrectomies were plated on frozen sections of caudate nucleus and heart, and on polylysine-coated slides, and were maintained for up to 3 weeks in medium with nerve growth factor to induce neurite outgrowth and cytosine arabinoside to prevent proliferation of other cell types. Additional cultures maintained for up to 3 weeks in nerve growth factor without tissue sections were trypsinized to remove processes and replated on frozen sections or polylysine to evaluate process regeneration. Processes were quantitated after visualization by glyoxylic acid-induced fluorescence. No more than 14% of cell clusters formed processes longer than 100 microns on caudate nucleus, versus 24% on heart and up to 84% on polylysine (all p less than .01). Comparable patterns were obtained for neurite regeneration. Our findings suggest that human brain tissue is for the most part inhospitable to neurites produced by sympathoadrenal cells, and that even tissues normally innervated by such cells are less hospitable than synthetic substrates. These findings might have important implications for future studies related to chromaffin cell transplantation.
Flaris
N
N
Department of Pathology, Tufts University, School of Medicine, Boston, Massachusetts.
Tischler
A S
AS
D000328:Adult; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000648:ultrastructure*; D003584:Cytological Techniques; D006801:Humans; D009416:Nerve Regeneration; D011107:Polylysine
D011107:Polylysine