TB-500 Peptide (TB4) 10MG

This 2010 paper in the Annals of the New York Academy of Sciences (Philp and Kleinman, National Institute of Dental and Craniofacial Research, NIH) reviews published animal studies of thymosin β4. It is a review article, not a single experiment. It summarizes topical studies in eye and skin wound models, and systemic studies in heart, brain, sepsis and autoimmune models, mostly in mice and rats, with one study in pigs.

Scope: The review covers animal and cell research on thymosin β4.

Note on terminology: The review studies thymosin β4. It does not use the name "TB-500". It notes that full-length synthetic and recombinant Tβ4, and one shorter Tβ4-derived peptide containing the actin-binding site, were each active in mouse skin-wound models.

• Citation: Philp D, Kleinman HK. Ann N Y Acad Sci. 2010;1194:81–86.
• Article type: Review of published animal studies
• Species covered: Mice and rats, plus a pig cardiac model and a sheep reperfusion model
• Topical models: Corneal injury, skin (dermal) wounds, hair regrowth
• Systemic models: Coronary ligation, cardiac reperfusion, brain injury, endotoxin shock, experimental autoimmune encephalomyelitis
• Author disclosure: One author reported consulting for RegeneRx Biopharmaceuticals, a company developing thymosin β4.

Tβ4 is the main actin-sequestering molecule in mammalian cells. By binding actin, it influences cell shape and movement. The review notes that, unlike classic growth factors, Tβ4 does not itself promote cell growth and does not bind heparin, which lets it diffuse into tissues. It is also smaller: 4,964 Da, compared with about 14,000–16,000 Da for typical growth factors.

Tβ4 is present in wound fluid and is released by platelets, which are among the first cells to reach a site of injury. In cell and animal studies, the authors list several reported activities:

• Promotion of cell migration, including re-epithelialization
• Formation of new blood vessels (angiogenesis)
• Reduced levels of some inflammatory cytokines and chemokines
• Reduced cell death (anti-apoptotic activity) in some models
• Effects on stem and progenitor cell migration and differentiation
• Reduced fibrosis in some cardiac and neural models

Corneal injury: In rat and mouse corneas injured with heptanol or alkali, topical Tβ4 (5 µg in 5 µL, twice daily) was associated with faster re-epithelialization. In the alkali model, it was associated with lower inflammatory markers. Reported mechanisms included reduced matrix metalloproteinase activity, reduced TNF-α-driven cytokine release and NF-κB activation, and increased laminin-5. The review notes that Tβ4 did not induce new blood vessels in the cornea.

Skin wounds: In full-thickness punch wounds in rats and mice, topical Tβ4 (5–50 µg per wound) was associated with faster wound closure, more collagen deposition and more angiogenesis. This included models of impaired healing, such as diabetic (db/db) mice, aged mice and steroid-treated rats.

Hair regrowth: An unexpected observation in the skin studies was increased hair growth near treated wounds. Follow-up studies in shaved rats and mice applied Tβ4 in a hydrogel every other day. Cell studies suggested this involved migration and differentiation of hair follicle stem cells, activating existing follicles rather than forming new ones.

Systemic doses in the reviewed studies ranged from 400 ng per animal (intracardiac administration in mice) to 15 mg per animal (retroinfusion in pigs of about 25 kg):

• Heart: In a mouse coronary ligation model, Tβ4 was associated with better cardiomyocyte survival and cardiac function. The proposed mechanism involved integrin-linked kinase (ILK) and Akt activation. In a pig reperfusion model, it was associated with smaller infarct size and less inflammatory cell influx.
• Brain: In rats, Tβ4 delivered into the brain ventricles twice daily for 5 days was associated with less hippocampal neuron loss after kainic acid injury.
• Autoimmune encephalomyelitis: In mice with this model of central nervous system inflammation, intraperitoneal Tβ4 was associated with functional recovery, less inflammation and more mature oligodendrocytes.
• Endotoxin shock: In rats given a lethal dose of bacterial lipopolysaccharide, Tβ4 at 0, 2 and 4 hours was associated with lower mortality and lower inflammatory cytokines.

The review cites nonclinical toxicology studies in which intravenous Tβ4 was well tolerated in rats, dogs and monkeys across the dose ranges tested. The cited source describes these studies as part of Tβ4 drug development (Crockford, 2007). They do not establish the safety of any other material, route or species.

• This is a narrative review, not a systematic review or meta-analysis. Each finding comes from a separate study with its own design and sample size.
• Most studies used full-length thymosin β4. Results may not apply to shorter fragments or other materials sold under the name TB-500.
• Many studies came from a small number of laboratories, and one author disclosed a consulting relationship with a company developing Tβ4.
• Tβ4 has also been studied in relation to tumor cell motility and metastasis, which the review cites in its reference list.
• Animal findings do not establish effects, safety or dosing in people.

Philp and Kleinman (2010) summarize animal research in which thymosin β4 was associated with faster corneal and skin wound closure, more angiogenesis, hair-follicle activation, and reduced cell loss or inflammation in cardiac, neural and sepsis models. The authors attribute these observations to Tβ4's roles in cell migration, inflammation, cell survival and stem-cell differentiation, while noting that much remains to be learned about its mechanisms.

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