Microvascular free flaps for local or systemic delivery

摘要

The present invention relates to methods of ex-vivo modification of mammalian tissue, via genetic transformation or introduction of cells, followed by implantation of the modified tissue into a patient in need thereof. Preferably, the tissue is microvascular free flap (or microvascular bed) tissue. A tissue explant is detached from the native circulation of a donor, transfected ex vivo, and then attached (anastomosed) to a recipient, either the donor or another patient. In a preferred embodiment, the mammalian tissue is human tissue and the patient is a human patient. Transfection with a nucleic acid encoding a product of interest is performed by contacting the selected tissue with a vector, preferably a viral vector, most preferably an adenoviral vector, that comprises the nucleic acid encoding the product of interest. The nucleic acid encoding the product of interest is driven by regulatory element such as an inducible, constitutive or cell-specific promoter, preferably an inducible or constitutive promoter. After genetic transformation of the selected tissue, the tissue is flushed to remove the vector not incorporated into the cells of the tissue. The tissue is then attached to the native circulation of the recipient using microvascular techniques. In one aspect, the invention provides methods of local delivery of a product (protein) of interest. In another aspect, the invention provides methods of systemic delivery of a product of interest. In yet another aspect, the invention provides methods of both local and systemic delivery of a product of interest. In yet another aspect, the invention provides methods for producing a neo-organ, i.e., a non-naturally occurring vascularized tissue that provides a function of a gland or organ, or that supplements the function of a gland or organ, and that delivers locally or systemically a product of interest to a patient in need thereof.