Efficient transmicrocatheter delivery of functional fibroblasts with a bioengineered collagen gel-platinum microcoil complex: toward the development of endovascular cell therapy for cerebral aneurysms.
OBJECTIVE
Endoaneurysmal implantation of fibroblasts may promote healing of aneurysms and reduce recanalization after therapeutic embolization. The purpose of our study was to develop a device for delivery of fibroblasts with use of current microcoil technology.


METHODS
Cell carrier devices and cell-free devices were fabricated by associating collagen gels (with or without fibroblasts) with platinum microcoils. During the propagation of control cell carrier devices for 1 week in culture, cell-mediated gel contraction (CMGC) occurred. Modified cell carrier devices created by glutaraldehyde cross-linking, ascorbate coculture, or extended CMGC were also characterized in vitro. Devices were deployed through microcatheters (533 microm lumen, 160 cm length). Gel retention, cell retention, cell death, and the ability to support local cell migration were analyzed in vitro.


RESULTS
Cell viability was reduced by glutaraldehyde cross-linking but not by microcatheter transit. During microcatheter transit, cell carrier devices liberated minimal particulate matter and cellular DNA. Liberated particulate matter was reduced by glutaraldehyde cross-linking (P < .05) and extended CMGC (P < .04). Only cell carrier devices treated with glutaraldehyde cross-linking did not exhibit cell migration after microcatheter transit. Passage of cell-free devices through microcatheters sheared off most of their collagen gel.


CONCLUSIONS
Collagen gel-platinum microcoil complexes can mediate efficient transmicrocatheter delivery of viable, migration-capable fibroblasts. CMGC is a necessary component of the process of gel stabilization that enables successful microcatheter transit. Although extended CMGC and glutaraldehyde cross-linking enhance gel stabilization, glutaraldehyde cross-linking decreases cell viability and migratory potential.
Abruzzo
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Section of Interventional Neuroradiology, Department of Radiology and The Neuroscience Institute, University of Cincinnati Medical Center, Cincinnati, Ohio, USA. editor@mayfieldclinic.com
Tun
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T
Sambanis
A
A
D001698:Biomedical Engineering; D002404:Catheterization / Q000295:instrumentation*; D016923:Cell Death; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004396:Coloring Agents; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D005782:Gels / Q000737:chemistry; D005976:Glutaral / Q000494:pharmacology; D006801:Humans; D002532:Intracranial Aneurysm / Q000601:surgery; D010984:Platinum; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D003432:Cross-Linking Reagents; D005782:Gels; D013778:Tetrazolium Salts; D013844:Thiazoles; D010984:Platinum; D003094:Collagen; D004247:DNA; C022616:thiazolyl blue; D005976:Glutaral