Linked Life Data

8338876

Source:http://linkedlifedata.com/resource/pubmed/id/8338876

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-9-2
pubmed:abstractText
Deficiency of clotting factor IX (FIX) causes hemophilia B in humans. We propose a novel approach to its treatment by engineering FIX-secreting cell lines suitable for implantation in different allogeneic hosts. To prevent graft rejection following implantation, the recombinant cells can be protected with biocompatible membranes that permit exit of FIX but not entry of cellular immune mediators. To explore the feasibility of this approach, we now report on the creation of mouse Ltk- fibroblast cell lines that can deliver FIX through such immune-protective membranes. Mouse fibroblasts (Ltk-) were transfected with the cDNA for human FIX and clones secreting high levels of FIX were isolated. About 70% of the secreted FIX was biologically active. Over 98% of the recovered biological activity was precipitable by barium citrate, indicating appropriate. gamma-carboxylation of the secreted FIX. The secreted FIX was similar in molecular weight and immunoreactivity to plasma-derived human FIX. Upon enclosure in microcapsules fabricated from the biocompatible polymers, alginate-polylysine-alginate, the cells survived the encapsulation procedure with about 70-90% viability, proliferated within the microcapsules to twice their original number within 2 weeks, and continued to secrete FIX into the culture medium at similar rates as the unencapsulated cells. The biological activity, degree of post-translational gamma-carboxylation, and immunoreactivity of the FIX recovered from the culture media of the encapsulated cells were identical to those of the FIX secreted by the unencapsulated cells. In conclusion, fibroblasts engineered to secrete recombinant human FIX can proliferate and continue to secrete biologically active FIX through the alginate microcapsules. This demonstrates the feasibility of using microencapsulated recombinant cells to deliver human FIX and the potential for allogeneic somatic gene therapy for hemophilia B.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
291-301
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Expression of human factor IX by microencapsulated recombinant fibroblasts.
pubmed:affiliation
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't