Correction of the growth defect in dwarf mice with nonautologous microencapsulated myoblasts - An alternate approach to somatic gene therapy

Ayman Al-Hendy, Gonzalo Hortelano, Gloria S. Tannenbaum, Patricia L. Chang

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Most of the currently approved human gene therapy protocols depend on genetic modification of autologous cells. We propose an alternate and potentially more cost-effective approach by implanting genetically modified 'universal' cell lines to deliver desired gene products to nonautologous recipients. The recombinant allogeneic cells are protected from rejection after implantation by enclosure within immune-protective alginate-poly-L-lysine-alginate microcapsules. The clinical efficacy of this strategy is now demonstrated by implanting microencapsulated allogeneic myoblasts engineered to secrete mouse growth hormone into the growth hormone-deficient Snell dwarf mice. The treated mutants attained increases in linear growth, body weights, peripheral organ weights, and tibial growth plate thickness significantly greater than those of the untreated controls. Secondary response to the exogenous growth hormone stimulation also resulted in increased fatty acid metabolism during the first month post-implantation. The microcapsules retrieved after about 6 months of implantation appeared intact. The encapsulated myoblasts retained a viability of > 60% and continued to secrete mouse growth hormone. Thus, implantation of nonautologous recombinant cells corrected partially the pleiomorphic effects of a transcription factor mutation in the Snell dwarf mice and the encapsulated cells remained functional for at least 6 months. This simple method of delivery recombinant gene products in vivo is a benign procedure, obviates the need for patient-specific genetic modification, and is amenable to industrial-scale quality control. It should have wide applications in therapies requiring a systemic continuous supply of recombinant gene products.

Original languageEnglish
Pages (from-to)165-175
Number of pages11
JournalHuman Gene Therapy
Volume6
Issue number2
Publication statusPublished - Feb 1995
Externally publishedYes

Fingerprint

Myoblasts
Genetic Therapy
Growth Hormone
Growth
Capsules
Genes
Growth Plate
Organ Size
Quality Control
Transcription Factors
Fatty Acids
Body Weight
Costs and Cost Analysis
Cell Line
Mutation
alginate-polylysine-alginate
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Correction of the growth defect in dwarf mice with nonautologous microencapsulated myoblasts - An alternate approach to somatic gene therapy. / Al-Hendy, Ayman; Hortelano, Gonzalo; Tannenbaum, Gloria S.; Chang, Patricia L.

In: Human Gene Therapy, Vol. 6, No. 2, 02.1995, p. 165-175.

Research output: Contribution to journalArticle

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