Thymosin β4 (TB‑500): Enhancing Angiogenesis & Tissue Repair via EPCs and Wound Healing Models

Study 1: Thymosin β4 promotes survival and angiogenesis of endothelial progenitor cells in infarcted myocardium

Quan Z. et al., International Journal of Molecular Medicine, April 2017 – Rats, myocardial infarction model PubMed+PMC

Summary

This in vivo/in vitro study evaluated the impact of Thymosin β4 (Tβ4) on endothelial progenitor cells (EPCs) in rat myocardial infarction (MI) models. Bone-marrow‑derived EPCs were pretreated with Tβ4 at 0.05, 0.1, and 0.2 µM concentrations before being transplanted into ischemic rat hearts. Researchers assessed cell viability (MTT assay), migration (Transwell), and angiogenesis (tube formation in Matrigel), under hypoxia and serum-deprivation conditions. Tβ4 significantly enhanced EPC survival, reduced apoptosis, improved migration, and increased tube formation; these effects correlated with elevated phospho‑Akt (p‑Akt) signaling. Four weeks post-transplantation, cardiac function improved, infarct size decreased, and microvessel density rose in treated groups compared to controls. Tβ4 demonstrated dose‑dependent cytoprotective and pro‑angiogenic effects, likely mediated via the Akt pathway PMC+PubMed.

Research Highlights

• Improved EPC viability and reduced apoptosis under ischemic stress

• Enhanced EPC migration and angiogenesis

• Cardiac function recovery and reduced scar tissue formation in rat MI model

• Akt phosphorylation as a central signaling mechanism

Research Applications

Suitable for studies evaluating EPC function, hypoxia resilience, or angiogenic therapies. TB‑500’s ability to enhance cell survival and induce microvascular repair underscores its relevance for clinical-model studies involving ischemic injury or regenerative protocols.

Study 2: Tβ4 promotes angiogenesis via VEGF-dependent EPC paracrine signaling

Spandidos et al., Molecular Medicine Reports, 2018 – Tube formation assay + VEGF mediation in vitro and rat EPC transplants PubMed+ Spandidos Publications

Summary

Investigating how Tβ4 enhances EPC-mediated angiogenesis, this in vitro and in vivo analysis measured VEGF-mediated paracrine secretion. Tβ4 pretreatment significantly increased VEGF secretion from EPCs, confirmed by ELISA and tube formation assays (HUVEC cells). Blocking VEGF neutralized angiogenic benefit, demonstrating VEGF’s pivotal role. Rats receiving Tβ4-pretreated EPCs exhibited significantly higher VEGF expression in infarct-border zones. Inhibition of the Akt/eNOS pathway (via siRNA knockdown) reduced VEGF release, linking the signaling cascade to paracrine-driven angiogenesis PubMed.

Research Highlights

• Tβ4-enhanced VEGF secretion drives angiogenesis in vitro

• VEGF-neutralizing antibodies block angiogenic effects

• In vivo rat myocardial model confirmed increased VEGF in treated groups

• Akt/eNOS signaling identified as key regulatory pathway

Research Applications

Ideal for experimentally exploring paracrine mechanisms, VEGF regulation, and endothelial cell function. Silent VEGF-dependence and Akt/eNOS involvement support research into vascular regeneration and signal transduction.

Study 3: Rat palatal mucosa wound healing: MMP2 and VEGF expression responses to Tβ4

International Journal of Molecular Medicine, 2014 – Rat palatal cell model PubMed

Summary

This cellular study measured VEGF and MMP2 gene and protein expression in rat palatal mucosal cells treated with 1,000 ng/mL Tβ4. After 6 hours, VEGF mRNA increased ~1.4-fold, and MMP2 mRNA levels spiked—effects reversed at 24 hours. Protein levels showed dose-dependent increases: VEGF protein doubled and pro-/active MMP2 rose 3.8‑ and 1.3‑fold, respectively. These findings suggest Tβ4 modulates extracellular matrix remodeling, migration, and angiogenic gene regulation Spandidos Publications.

Research Highlights

• Time-dependent upregulation of VEGF and MMP2 transcription

• Dose-responsive protein expression (Western blot confirmation)

• Molecular linkage between Tβ4 exposure and ECM‑remodeling pathways

Research Applications

Valuable for wound repair, cell migration, or ECM remodeling research. Ideal for cellular assays analyzing gene regulation and protease-mediated tissue engineering.

Study 4: Tβ4 accelerates wound repair and angiogenesis in full-thickness rat skin wounds

Philp D. et al., The FASEB Journal, 2001 – Rat model of skin wound healing PubMed+Spandidos Publications+ncbi.nlm.nih.gov

Summary

This in vivo study used a rat full-thickness skin wound model to evaluate Tβ4’s effects on epithelial healing. Topical or intraperitoneal administration of Tβ4 increased reepithelialization by 42% at day 4 and up to 61% by day 7 compared to saline controls. Wound contraction measured 11% greater in treated rats. Enhanced collagen deposition and angiogenesis were observed, and keratinocyte migration assays (Boyden chamber) showed a 2–3× increase at minimal Tβ4 concentrations (10 pg). Results indicate Tβ4’s multi-modal wound repair activity PubMed.

Research Highlights

• Accelerated wound closure and reepithelialization

• Enhanced keratinocyte motility with low doses

• Increased collagen deposition and angiogenic signaling

Research Applications

Perfect for research on dermal regeneration, epithelial migratory dynamics, or inflammatory repair. Offers model data for dose‑response studies and tissue-level healing assays.

⚠️ Research Disclaimer

All summarized studies are provided strictly for research purposes. None imply or endorse clinical or human use. ExoLabz peptides are sold only for laboratory research, with strict disclaimers: “For Research Use Only — Not for Human or Veterinary Use”.