Dose control with cell lines used for encapsulated cell therapy.
Cell therapy-use of cells to deliver active factors-is an emerging technique in treatment of neurodegenerative disease. Successful devices maintain cell viability and functionality over extended implant periods. Use of dividing cell lines to deliver therapeutic factors has been studied extensively. One emerging issue is the tendency of cells to continue proliferation within the intracapsular environment-potentially outstripping nutrient supply. This work presents a method of controlling proliferation and delivering therapeutic molecules within a dose range. The method entails encapsulation into a hollow fiber device of discrete numbers of cell-containing microcarriers. Proliferation control is attained by embedding cell-containing microcarriers in nonmitogenic hydrogels. PC-12 cells secreting L-dopa and dopamine was the model cell line tested. Feasibility of the method in controlling growth of normally rapidly dividing cells in the intracapsular environment was demonstrated in vitro and in vivo. Control nonmicrocarrier PC-12 cell devices had approximately fourfold greater expansion in cell number compared to experimental microcarrier-containing devices over 4 weeks in vitro and in vivo after implant into rat striatum. Ability to control dose released over a several-fold range was demonstrated with encapsulated PC-12 cells delivering neurotransmitters and C2C12 mouse myoblast cells delivering neurotrophic factors (CNTF).
Li
R H
RH
Genetics Institute, One Burtt Rd, Andover, MA 01810, USA. rli@genetics.com
Williams
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S
White
M
M
Rein
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D000818:Animals; D002455:Cell Division; D017690:Cell Transplantation; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D003342:Corpus Striatum; D015194:Diffusion Chambers, Culture; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005240:Feasibility Studies; D020100:Hydrogels; D051379:Mice; D008863:Microspheres; D018482:Muscle, Skeletal / Q000166:cytology*; D016716:PC12 Cells / Q000378:metabolism / Q000637:transplantation*; D010300:Parkinson Disease / Q000601:surgery; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D016042:Transplantation, Heterotopic / Q000379:methods*
D020934:Ciliary Neurotrophic Factor; D020100:Hydrogels; D002686:Chitin; D004295:Dihydroxyphenylalanine; D048271:Chitosan; D004298:Dopamine