How does it work?
Thymosin beta-4 binds to actin, a building material inside cells that controls how cells change shape and move. By affecting actin, researchers have seen that Tβ4 can make it easier for cells to migrate towards areas of injury. In laboratory and animal experiments, the substance has also been linked to the formation of new blood vessels (angiogenesis), dampening of inflammation and less cell death. TB-500 is regarded as the part of Tβ4 that contains this actin-binding region, and is thought to account for much of the activity.
Technical mechanism
Described in the research literature as a synthetic fragment of an actin-binding region of Thymosin Beta-4. Ac-SDKP is another fragment. Preclinical studies of the parent protein and selected fragments investigate, among other things, cell migration and angiogenesis. The results apply to the molecule that was studied, not automatically to the product.
What is being researched?
- Cell movement (migration) of skin and blood vessel cells
- Wound and skin healing in experimental models
- Formation of new blood vessels (angiogenesis)
- Repair of heart tissue after a heart attack (in animal experiments)
- Repair of the cornea and dry eyes (human studies on Tβ4/RGN-259)
- Nerve tissue after brain injury and stroke (in animal experiments)
About the evidence: Much of the research has been done on the parent protein thymosin beta-4, not directly on the TB-500 fragment, and most of the evidence on muscle, tendon and skeletal repair is preclinical (cell and animal experiments). There are some human studies, but most concern Tβ4 given as eye drops (RGN-259) for dry eyes and corneal damage – not TB-500 used on muscle or skeleton. Results from cells and animals cannot be transferred directly to humans. The content is intended as research background only, not as health advice.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
Cell migration, wound and skin healing
Studies have investigated how thymosin beta-4 affects cells' ability to move, and how the substance influences healing of skin and wounds in experimental models. This work underpins the interest in tissue repair.
- Thymosin beta4 accelerates wound healing PreclinicalPubMed· 1999
In this animal study in rats, thymosin beta4 accelerated the healing of skin wounds. The wounds closed faster, contracted more and gained more connective tissue and more new blood vessels. In the laboratory, the substance also made skin cells move faster. This is an animal and laboratory study, and the results cannot be transferred directly to humans.
- Thymosin β4 Promotes Dermal Healing ReviewPubMed· 2016
This review summarises research on thymosin beta4 and wound healing in the skin. The substance occurs naturally in the body and is described as anti-inflammatory and as promoting new blood vessels. The authors describe that it accelerated healing in several animal models, and in phase 2 studies in patients with pressure ulcers, leg ulcers and the skin disease epidermolysis bullosa, with good tolerability. This is a summary article.
Angiogenesis and blood vessels
Research has explored how Tβ4 affects the formation of new blood vessels and the movement of the cells that build them. Much of this has been done in cell and tissue experiments.
- The actin binding site on thymosin beta4 promotes angiogenesis PreclinicalPubMed· 2003
In this laboratory experiment, the researchers investigated which part of thymosin beta4 enables it to form new blood vessels. They found that a short stretch of seven amino acids, which binds to the protein actin, is necessary for this effect. Parts without this stretch had no effect. This is a laboratory experiment on cells and tissue, not in humans.
- Thymosin beta4 induces endothelial progenitor cell migration via PI3K/Akt/eNOS signal transduction pathway PreclinicalPubMed· 2009
In this laboratory experiment, thymosin beta4 made a type of blood vessel precursor cell move more, depending on the dose. The effect went through a specific signalling pathway in the cells; when the researchers blocked it, the effect disappeared. Another signalling pathway was less important. This is a laboratory experiment on cells and says nothing about effects in humans.
- Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease ReviewPubMed· 2018
This review summarises the role of thymosin beta4 in the development, repair and protection of blood vessels. The authors describe that the substance is involved in several processes that form and stabilise blood vessels, and that added substance increases the formation of small blood vessels in experiments. They emphasise that the underlying mechanisms are still unclear. This is a summary article.
Repair of heart and nerve tissue (experimental models)
In animal experiments, researchers have studied whether Tβ4 can affect the repair of heart tissue after infarction, and recovery of function after brain injury and stroke. This is preclinical research on the parent protein.
- Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction PreclinicalPMC· 2014
In this animal study in mice with heart attack, thymosin beta4 reduced the risk of the heart rupturing, partly through less inflammation and fewer dying heart cells. Five weeks of treatment improved the heart's pumping function, reduced scarring and increased the number of small blood vessels. Fewer animals died. This is an animal study, and the results cannot be transferred directly to humans.
- Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction PreclinicalPMC· 2021
In this animal study in pigs with heart attack, heart muscle cells made from stem cells were placed into the heart. On their own the cells survived poorly, but together with thymosin beta4, delivered from small gel beads, more cells engrafted, new blood vessels formed, pumping function improved and the infarct was smaller. The treatment appeared to be safe in the experiment. This is an animal study with no direct transferability to humans.
- Neuroprotective and neurorestorative effects of Thymosin beta 4 treatment following experimental traumatic brain injury PreclinicalPMC· 2012
This article discusses thymosin beta4 as a possible candidate for treating traumatic brain injury. The authors point out that the body has a limited ability of its own to repair the brain after such injury, and that in experiments the substance promotes, among other things, new blood vessels, nerve cells and reduced cell death and inflammation. This is based on animal and laboratory research, not studies in humans.
- Thymosin β4 improves functional neurological outcome in a rat model of embolic stroke PreclinicalPMC· 2010
In this animal study in rats with stroke, thymosin beta4 was given from one day after the stroke. The treated rats had clearly better function in tests of movement and sensation. The injured area itself did not become smaller, but there were more blood vessels and more rebuilding of the insulating layer around nerve fibres. This is an animal study with no direct transferability to humans.
Eye and corneal repair (human studies on Tβ4)
Here are some of the few human studies on Tβ4: given as eye drops (RGN-259), the substance has been investigated in controlled studies on dry eyes and corneal damage. Note that this concerns the parent protein as eye drops, not TB-500 for muscle/skeleton.
- Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial Clinical (human)PubMed· 2015
In this small phase 2 study, nine patients with severe dry eyes received either eye drops containing thymosin beta4 (RGN-259) or placebo drops. Those who received the active substance had less discomfort and less damage to the cornea, and a better tear film. The drops were well tolerated. The study was small. This describes what the researchers observed, and is not a treatment recommendation.
- 0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial Clinical (human)PMC· 2023
In this phase 3 study, patients with nerve impairment of the cornea received either eye drops containing thymosin beta4 (RGN-259) or placebo drops. More people in the treatment group had their corneal wounds heal completely, and they reported less discomfort, dryness and foreign-body sensation. No serious side effects were seen. This describes what the study observed, not a treatment recommendation.
- RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model PreclinicalPMC· 2018
In this animal study in mice with dry eyes, RGN-259 (thymosin beta4) was compared with three prescription medicines. The substance increased tear production, made the cornea smoother, reduced inflammation and increased mucus-producing cells. On several measures it was as good as or better than the other medicines. This is an animal study with no direct transferability to humans.