Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats.
Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by interfacial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatal implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamine for at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-beta-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.
Aebischer
P
P
Section for Artificial Organs, Biomaterials and Cellular Technology, Brown University, Providence, RI.
Tresco
P A
PA
Sagen
J
J
Winn
S R
SR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002838:Chromaffin System / Q000166:cytology* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004339:Drug Compounding; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation; D013239:Stereotyped Behavior / Q000502:physiology*; D016378:Tissue Transplantation
D002395:Catecholamines; D016627:Oxidopamine; D001058:Apomorphine