Growth Retardation—An Unexpected Outcome from Growth Hormone Gene Therapy in Normal Mice with Microencapsulated Myoblasts

摘要: Recently, we have succeeded in using nonautologous myoblasts engineered to secrete mouse growth hormone (GH) correct partially the retardation of Snell dwarf mice, which suffer from pituitary GH deficiency. The allogeneic were protected immune rejection by enclosure permselective microcapsules fabricated alginate, thus validating clinical efficacy universal cells for somatic gene therapy. Because therapy is considered also treating patients with normal function, now apply this protocol treat mice evaluate potential consequences subjects no demonstrated When microencapsulated implanted into male and female contrary expectation, treated animals became significantly shorter lost weight; their internal organs smaller tibial plates less differentiated, indicating reduced skeletal growth. Females more severely affected than males 2 died day 13 unknown cause. By 70, most abnormalities restored except body weights, remained below normal. In conclusion, although delivery beneficial dwarfism, it may adverse metabolic those hypothalamic-pituitary functions, males.