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Systemically administered, yet target organ-specific therapies for tissue regeneration

Tero Järvinen, M.D., Ph.D is a Professor and Chief Surgeon at the Tampere University and Tampere University Hospital, Finland. He graduated from the Medical School, University of Tampere in 1997 and completed his PhD in 1999 from University of Tampere, Finland. He completed his training in clinical medicine (orthopedic surgery and traumatology) in 2008. Tero Järvinen joined the lab of Professor Erkki Ruoslahti at the Sanford Burnham Prebys Medical Discovery Institute (SBPMDI) at La Jolla, CA, USA from 2003 - 2006 as a postdoctoral fellow. After returning back to Finland, Prof. Tero Järvinen founded the laboratory of Regenerative Medicine at the Tampere University. The main focus of the research is to develop systematically administered, target-seeking therapeutic molecules for the regenerative medicine. These novel targeted molecules would have increased therapeutic value in the diseased organ compared to the conventional therapeutics while simultaneously reducing the harmful side-effects in the normal tissues.

The approach is based on the fact that the blood vessels in each tissue have a unique molecular fingerprint that is specific for that given tissue, i.e. vascular “Zip code”. Furthermore, human diseases also cause molecular changes (induced expression of specific cell surface markers) in the blood vessels supplying the involved organ. For example, angiogenic blood vessels in tumors and in regenerating tissues express distinctive markers that are not present in vessels of normal tissues. These specific cell surface markers, in turn, can be specifically targeted by vascular homing peptides that home to their target organ when administered systemically. Dr. Järvinen's research group has identified vascular homing peptides that specifically target the angiogenic blood vessels and the vasculature inflammatory diseases. Utilizing these target-tissue specific homing peptides, they have devised two novel delivery mechanisms:

A) building multi-functional fusion-proteins (CAR-decorin) consisting of separate domains for targeting and tissue penetration and therapeutic effects. CAR-decorin is a systemically administered, target-seeking biotherapeutic that inhibits scar formation. The injury can happen in any organ of the body (or multiple organs simultaneously) and systemically administered vascular homing peptide CAR can be found there through blood stream by targeting angiogenic vasculature forming at the site of the injury. CAR-decorin binds to its receptor specific for the vasculature of the injured tissues and extravasates into surrounding tissue, where it binds to its receptor on the cell surface of the scar producing fibroblasts. The CAR binding to the HSPGs provides ideal docking for the therapeutic part of the molecule, decorin, for binding and neutralization of its molecular targets; TGF-b1 and -b2, the growth factors responsible for scar formation. The clinical outcome is reduced scarring.

B) recently published revolutionary tissue-penetrating transport pathway called “bystander effect”, to target the drugs without conjugating them to the delivery vehicle. The “bystander effect” provides the advantage of promoting delivery of a drug to its target tissue without the need of coupling of the drug to the peptide required in conventional drug targeting.

Web page: https://research.tuni.fi/regenerative-medicine-lab/

Selected publications:

Screening of homing and tissue-penetrating peptides by microdialysis and in vivo phage display. Pemmari, T. et al., Life Sci Alliance. 2025.

https://pubmed.ncbi.nlm.nih.gov/39933917/

Histological Definition of Skeletal Muscle Injury: A Guide to Nomenclature Along the Connective Tissue Sheath/Structure. Pedret, C. et al., Sports Med. 2024.

https://pubmed.ncbi.nlm.nih.gov/39692975/

Myofibroblasts reside in the middle dermis of the keloids but do not predict the response to injection therapies: a double-blinded, randomized, controlled trial.

Komulainen, T. et al., Front Med (Lausanne). 2024. https://pubmed.ncbi.nlm.nih.gov/38495113/

Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function. 

Maldonado, H. et al., Nat Commun. 2023. https://pubmed.ncbi.nlm.nih.gov/38057316/