title: Systemically Administered, Target Organ-Specific Therapies for Regenerative Medicine.
abstract: Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues. Although human diseases are treated with systemically administered drugs in general, all current efforts aimed at enhancing tissue repair with biological drugs have been based on their local application. The systemic administration of growth factors has been ruled out due to concerns about their safety. These concerns are warranted. In addition, only a small proportion of systemically administered drugs reach their intended target. Selective delivery of the drug to the target tissue and use of functional protein domains capable of penetrating cells and tissues could alleviate these problems in certain circumstances. We will present in this review a novel approach utilizing unique molecular fingerprints ("Zip/postal codes") in the vasculature of regenerating tissues that allows target organ-specific delivery of systemically administered therapeutic molecules by affinity-based physical targeting (using peptides or antibodies as an "address tag") to injured tissues undergoing repair. The desired outcome of targeted therapies is increased local accumulation and lower systemic concentration of the therapeutic payload. We believe that the physical targeting of systemically administered therapeutic molecules could be rapidly adapted in the field of regenerative medicine.
authors.affiliation: School of Medicine, University of Tampere, 33520 Tampere, Finland. blteja@uta.fi.|Department of Orthopedics & Traumatology, Tampere University Hospital, 33520 Tampere, Finland. blteja@uta.fi.
authors.forename: Tero A H
authors.initials: TA
authors.lastname: Järvinen
authors.affiliation: School of Medicine, University of Tampere, 33520 Tampere, Finland. ulrike.may@uta.fi.
authors.forename: Ulrike
authors.initials: U
authors.lastname: May
authors.affiliation: School of Medicine, University of Tampere, 33520 Tampere, Finland. stuart.prince@uta.fi.
authors.forename: Stuart
authors.initials: S
authors.lastname: Prince
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D024201:Bystander Effect; D016503:Drug Delivery Systems; D006801:Humans; D009928:Organ Specificity; D010455:Peptides / Q000378:metabolism; D044968:Regenerative Medicine / Q000379:methods*
chemical_list: D010455:Peptides
keywords: angiogenesis; decorin; in vivo phage display; regenerative medicine; tissue regeneration; vascular ZIP codes