title: Poly(vinyl alcohol) synthetic polymer foams as scaffolds for cell encapsulation.
abstract: Poly(vinyl alcohol) (PVA) foams were used as scaffolds in hollow fiber membrane-based cell encapsulation devices. The surrounding permselective membrane serves as an immunoisolation barrier while allowing metabolites and other small molecules to be freely transported. The internal matrix defines the microenvironment for the encapsulated cells. PC12 cell-containing devices represent one possible strategy for safe transplantation of dopamine-secreting cells for the treatment of dopamine-deficient diseases such as Parkinson's disease. PC12 cells--a dopamine-secreting cell line--were encapsulated with PVA foam as a matrix material in the lumen of these hollow fibers. In this work, we demonstrate the presence of the PVA matrix increased the catecholamine secretion efficiency of the cells as compared to devices containing a chitosan matrix. Devices were implanted in vivo into rodent striatum and device output of catecholamines was measured preimplant and post-explant. Evoked stores of dopamine remained constant (preimplant vs explant) for devices encapsulated with the foam matrix and increased with devices encapsulated with chitosan matrix. Cell proliferation within devices was inhibited in the presence of the foam matrix. Cell viability and distribution was significantly improved with the inclusion of the foam matrix in both in vitro and in vivo studies. In comparison to chitosan--a typical matrix material for PC12 cells--addition of a foam-type matrix altered the encapsulated cell microenvironment and resulted in more efficient secretion of catecholamines and improved distribution within the device resulting in smaller necrotic regions and a lower rate of cell proliferation.
authors.affiliation: CytoTherapeutics, Inc., Lincoln, RI 02865, USA. rhli@cyto.com
authors.forename: R H
authors.initials: RH
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: White
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Hazlett
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008567:Membranes, Artificial; D016716:PC12 Cells / Q000166:cytology / Q000637:transplantation; D010300:Parkinson Disease / Q000628:therapy; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008567:Membranes, Artificial; D002686:Chitin; D007980:Levodopa; D011142:Polyvinyl Alcohol; D048271:Chitosan; D004298:Dopamine