Abstract
Microencapsulation of recombinant 'universal' cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic gene products secreted by these cells can be delivered to different patients without immunosuppression or genetic modification of the host's cells. The encapsulation of different mammalian cell types (epithelial cells, fibroblasts, and myoblasts) is compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules with a solubilized core and a poly-L-lysine - alginate-taminated surface; (2) barium-linked alginate beads with a gelled core; and (3) a hybrid formulation of barium- linked alginate beads with a poly-L-lysine-alginate-laminated surface. The mechanical stability of the different microcapsule types, as measured with a cone-and-plate shearing apparatus, was superior in the two barium-linked alginate beads. All cell types maintained high viability (65-90%) in culture after encapsulation. The recombinant gene products secreted by these cells (human growth hormone MW = 22,000, human factor IX MW = 57,000, and murine β-glucuronidase MW = 300,000) were able to traverse the three microcapsule types at similar rates. Cell numbers within the microcapsules increased twofold to > 20-fold over 4 weeks, depending on the cell type. Epithelial and myoblast cell numbers were not affected by microcapsule formulation; however, fibroblasts proliferated the most in the calcium-linked alginate spheres. These results show that for culturing fibroblasts in a mechanically stable environment the classical calcium-linked microcapsules are adequate. However, where mechanical stability is a more critical requirement, the solid barium- linked gelled beads are more appropriate choices.
| Original language | English |
|---|---|
| Pages (from-to) | 587-596 |
| Number of pages | 10 |
| Journal | Journal of Biomedical Materials Research |
| Volume | 42 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Dec 15 1998 |
| Externally published | Yes |
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Keywords
- β- glucuronidase
- Factor IX
- Gene therapy
- Human growth hormone
- Immunoisolation
ASJC Scopus subject areas
- Biomedical Engineering
- Biomaterials
Cite this
Encapsulation of various recombinant mammalian cell types in different alginate microcapsules. / Peirone, Michael; Ross, Colin J D; Hortelano, Gonzalo; Brash, John L.; Chang, Patricia L.
In: Journal of Biomedical Materials Research, Vol. 42, No. 4, 15.12.1998, p. 587-596.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Encapsulation of various recombinant mammalian cell types in different alginate microcapsules
AU - Peirone, Michael
AU - Ross, Colin J D
AU - Hortelano, Gonzalo
AU - Brash, John L.
AU - Chang, Patricia L.
PY - 1998/12/15
Y1 - 1998/12/15
N2 - Microencapsulation of recombinant 'universal' cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic gene products secreted by these cells can be delivered to different patients without immunosuppression or genetic modification of the host's cells. The encapsulation of different mammalian cell types (epithelial cells, fibroblasts, and myoblasts) is compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules with a solubilized core and a poly-L-lysine - alginate-taminated surface; (2) barium-linked alginate beads with a gelled core; and (3) a hybrid formulation of barium- linked alginate beads with a poly-L-lysine-alginate-laminated surface. The mechanical stability of the different microcapsule types, as measured with a cone-and-plate shearing apparatus, was superior in the two barium-linked alginate beads. All cell types maintained high viability (65-90%) in culture after encapsulation. The recombinant gene products secreted by these cells (human growth hormone MW = 22,000, human factor IX MW = 57,000, and murine β-glucuronidase MW = 300,000) were able to traverse the three microcapsule types at similar rates. Cell numbers within the microcapsules increased twofold to > 20-fold over 4 weeks, depending on the cell type. Epithelial and myoblast cell numbers were not affected by microcapsule formulation; however, fibroblasts proliferated the most in the calcium-linked alginate spheres. These results show that for culturing fibroblasts in a mechanically stable environment the classical calcium-linked microcapsules are adequate. However, where mechanical stability is a more critical requirement, the solid barium- linked gelled beads are more appropriate choices.
AB - Microencapsulation of recombinant 'universal' cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic gene products secreted by these cells can be delivered to different patients without immunosuppression or genetic modification of the host's cells. The encapsulation of different mammalian cell types (epithelial cells, fibroblasts, and myoblasts) is compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules with a solubilized core and a poly-L-lysine - alginate-taminated surface; (2) barium-linked alginate beads with a gelled core; and (3) a hybrid formulation of barium- linked alginate beads with a poly-L-lysine-alginate-laminated surface. The mechanical stability of the different microcapsule types, as measured with a cone-and-plate shearing apparatus, was superior in the two barium-linked alginate beads. All cell types maintained high viability (65-90%) in culture after encapsulation. The recombinant gene products secreted by these cells (human growth hormone MW = 22,000, human factor IX MW = 57,000, and murine β-glucuronidase MW = 300,000) were able to traverse the three microcapsule types at similar rates. Cell numbers within the microcapsules increased twofold to > 20-fold over 4 weeks, depending on the cell type. Epithelial and myoblast cell numbers were not affected by microcapsule formulation; however, fibroblasts proliferated the most in the calcium-linked alginate spheres. These results show that for culturing fibroblasts in a mechanically stable environment the classical calcium-linked microcapsules are adequate. However, where mechanical stability is a more critical requirement, the solid barium- linked gelled beads are more appropriate choices.
KW - β- glucuronidase
KW - Factor IX
KW - Gene therapy
KW - Human growth hormone
KW - Immunoisolation
UR - http://www.scopus.com/inward/record.url?scp=0032534528&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032534528&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-4636(19981215)42:4<587::AID-JBM15>3.0.CO;2-X
DO - 10.1002/(SICI)1097-4636(19981215)42:4<587::AID-JBM15>3.0.CO;2-X
M3 - Article
VL - 42
SP - 587
EP - 596
JO - Journal of Biomedical Materials Research
JF - Journal of Biomedical Materials Research
SN - 0021-9304
IS - 4
ER -