Cells encapsulated in alginate: a potential system for delivery of recombinant proteins to malignant brain tumours.
Growth and progression of malignant brain tumours occurs in a micromilieu consisting of both tumour and normal cells. Several proteins have been identified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continuous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therapeutic importance. In this study we have investigated the growth characteristics of cells encapsulated in alginate, which represents a potential delivery system for recombinant proteins that may have antitumour effects. Three different cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, which is an immuno-isolating substance extracted from brown seaweed. The encapsulated cells were observed at specific intervals during a 4-month period after in vitro propagation and as transplants into the cortex of BD-IX rats. Morphological studies showed that encapsulated cells proliferated and formed spheroids within the alginate in the in vitro cultures and after implantation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltration of mononuclear cells was observed in the brain bordering the alginate beads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation. The majority of inflammatory cells were reactive microglia and invading monocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N2 and will retain their viability and proliferative capacity.
Read
T A
TA
Department of Anatomy and Cell Biology, University of Bergen, Norway. t-a.read@pki.uib.no
Stensvaag
V
V
Vindenes
H
H
Ulvestad
E
E
Bjerkvig
R
R
Thorsen
F
F
D016475:3T3 Cells; D000464:Alginates; D000818:Animals; D019149:Bioreactors; D001932:Brain Neoplasms / Q000628:therapy*; D002214:Capsules; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004337:Drug Carriers; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D051381:Rats; D014183:Transplantation, Heterologous
D000464:Alginates; D002214:Capsules; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid