Tissue-engineered skeletal muscle organoids for reversible gene therapy.
Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.
Vandenburgh
H
H
Department of Pathology, Brown University School of Medicine, Providence, RI 02906, USA.
Del Tatto
M
M
Shansky
J
J
Lemaire
J
J
Chang
A
A
Payumo
F
F
Lee
P
P
Goodyear
A
A
Raven
L
L
D000818:Animals; D001774:Blood Chemical Analysis; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D013006:Growth Hormone / Q000032:analysis / Q000235:genetics*; D006801:Humans; D051379:Mice; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology; D009924:Organ Culture Techniques / Q000379:methods; D016377:Organ Transplantation; D011863:Radioimmunoassay
D013006:Growth Hormone