In vitro effects of transcatheter injection on structure, cell viability, and cell metabolism in fibroblast-impregnated alginate microspheres.
OBJECTIVE
To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structure, cell viability, or metabolism.


METHODS
Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregnated alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcatheter injection on structure and cell viability (percentage of viable cells per microsphere) were correlated with microsphere size. Structural effects were analyzed by using light microscopy, and 7-day percentage (ratio of live cells to dead cells) cell viability was assessed with confocal microscopy and fluorescent staining. In a second series of experiments, the metabolism of small microspheres was studied during a course of 7 days by using a spectrophotometric bioanalyzer.


RESULTS
Transcatheter injection caused fracturing and/or fragmentation of large (800-1,000 microm) and medium (500-750 microm) microspheres, while small (250-400 microm) microspheres were structurally unaffected by transcatheter injection. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viability by 17%-23% in all size categories, it did not cause a detectable alteration in the rate of glucose metabolism.


CONCLUSIONS
Transcatheter injection was physiologically well tolerated by fibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of microspheres compromised the sequestration function of the microsphere vector.
Abruzzo
T
T
Section of Interventional Neuroradiology, Department of Radiology, Emory University School of Medicine, 1364 Clifton Rd NE, Atlanta, GA 30302, USA. tabruzz@emory.edu
Cloft
H J
HJ
Shengelaia
G G
GG
Waldrop
S M
SM
Kallmes
D F
DF
Dion
J E
JE
Constantinidis
I
I
Sambanis
A
A
D000464:Alginates; D000818:Animals; D002404:Catheterization; D002470:Cell Survival; D003584:Cytological Techniques / Q000379:methods*; D004621:Embolization, Therapeutic; D005347:Fibroblasts; D005947:Glucose / Q000378:metabolism; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007267:Injections / Q000379:methods*; D018613:Microscopy, Confocal; D008863:Microspheres; D011817:Rabbits
D000464:Alginates; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D005947:Glucose