Thymosin Beta-4 (TB-4)

Thymosin Beta-4 (TB-4) is a naturally occurring peptide composed of 43 amino acids. It is derived from the thymus gland and is found in high concentrations in platelets, wound fluid, and most tissues throughout the body, though it is absent in red blood cells.

It is believed to play a role in tissue regeneration, wound healing, and cell migration. Studies suggest that TB-4 promotes angiogenesis, reduces inflammation, and supports repair of damaged tissues, contributing to faster recovery following injury.

Thymosin beta-4 accelerates tissue repair by promoting cell migration, reepithelialization, and angiogenesis. Laboratory studies show that Tβ4 acts as a chemoattractant for endothelial and epithelial cells and speeds wound closure in animal wound models. Tβ4 also stimulates formation of capillary-like structures and increases endothelial progenitor cell viability, which supports new blood vessel growth. In cardiac models Tβ4 reduces myocyte death and activates reparative epicardial and progenitor programs that improve post-infarct remodeling ¹.

Clinical and translational research supports these effects in humans and disease models. A phase II trial of topical 0.1% Tβ4 (RGN-259) showed improved signs and symptoms in patients with dry eye and faster corneal epithelial healing. Small randomized and controlled studies and registered trials have tested Tβ4 formulations for nonhealing cutaneous wounds, venous stasis ulcers, and epidermolysis bullosa with evidence of enhanced wound closure compared with placebo. Overall, animal and human studies indicate Tβ4 promotes cell migration, angiogenesis, epithelial repair, and activation of reparative programs that together accelerate tissue healing ².

The peptide Thymosin beta‑4 (Tβ4) appears to be well tolerated in the limited human trials so far. In a Phase I study of recombinant human Tβ4 in healthy volunteers, adverse events were mild to moderate, and there were no dose-limiting toxicities or serious adverse events reported ³. In another human trial using a topical ophthalmic Tβ4 solution for dry‐eye syndrome, no significant adverse events occurred and no participants withdrew because of side effects ⁴.

However, the safety profile remains incomplete and raises some theoretical concerns. Because Tβ4 can stimulate angiogenesis and cell migration (mechanisms of wound and tissue repair), there is a theoretical risk that it could promote unwanted neovascularization or tumor growth—this caution is discussed particularly in the context of autoimmune disease and cancer models ⁵.

Thymosin β4 (Tβ4) binds to G-actin monomers inside cells, thereby regulating actin polymerisation and cytoskeletal dynamics. It also promotes repair by mobilising stem and progenitor cells, enhancing migration and differentiation, stimulating angiogenesis and reducing apoptosis and inflammation in tissue-injury models. At the molecular signalling level Tβ4 influences pathways such as ERK, AKT, NF-κB and MAPKs, modulates HIF-1α under hypoxia and interferes with SMO/GLI2 in certain fibrotic contexts ^{6, 7, 8}.

The FDA has not approved any systemic TB-4 product for human use; TB-4 has an orphan designation (neurotrophic keratopathy) but is not FDA-approved, and the FDA has flagged thymosin-β4 (fragment) and related peptides as bulk substances that present significant safety risks for compounding due to lack of human exposure/safety data ⁹. In sports, Thymosin-β4 and its derivatives (e.g., TB-500) are named on the WADA Prohibited List as growth-factor/peptide substances, and U.S. anti-doping bodies (e.g., USADA/PFL lists) treat thymosin-β4 among prohibited growth factors/modulators ¹⁰.