BPC-157 / TB-500 Blend

1. Studied for

   The one controlled human trial of thymosin beta-4, in an eye formulation

   Thymosin beta-4 has reached a randomized controlled trial in people, but only as eye drops for dry eye, a formulation and route unrelated to anything else on this page. The trial was single-center, prospective, double-masked and placebo-controlled, with 72 qualifying participants with moderate to severe dry eye split evenly between a thymosin beta-4 eye solution and placebo for 28 days. Neither of the 2 things the trial had committed to measuring in advance, eye discomfort score and staining of the lower cornea, differed significantly between the thymosin beta-4 group and the placebo group at the primary visit. This entry is here to record how far the molecule has actually been studied under controlled conditions, including where it failed to beat placebo. It concerns a topical eye product and says nothing about any other tissue, route or preparation. in people: a randomized, double-masked, placebo-controlled Phase II trial, 72 participants, topical eye solution Preclinical strong More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong. Open for the full finding and the paper it came from.

   In the literature

   The one controlled human trial of thymosin beta-4, in an eye formulation

   Thymosin beta-4 has reached a randomized controlled trial in people, but only as eye drops for dry eye, a formulation and route unrelated to anything else on this page. The trial was single-center, prospective, double-masked and placebo-controlled, with 72 qualifying participants with moderate to severe dry eye split evenly between a thymosin beta-4 eye solution and placebo for 28 days. Neither of the 2 things the trial had committed to measuring in advance, eye discomfort score and staining of the lower cornea, differed significantly between the thymosin beta-4 group and the placebo group at the primary visit. This entry is here to record how far the molecule has actually been studied under controlled conditions, including where it failed to beat placebo. It concerns a topical eye product and says nothing about any other tissue, route or preparation.^{References 1}

   Modelin people: a randomized, double-masked, placebo-controlled Phase II trial, 72 participants, topical eye solution

   Confidence: strong

   More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong.

   Source

   Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model. Clin Ophthalmol. 2015;9:877-884. doi:10.2147/OPTH.S80954. PMID: 26056426

   PubMed 26056426

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. PubMed efetch for PMID 26056426 returned Clin Ophthalmol. 2015 May 20;9:877-84, doi:10.2147/OPTH.S80954, PMCID PMC4445951, authors Sosne G (Kresge Eye Institute, Wayne State University) and Ousler GW (Ora Inc), with the structured abstract, from which 2 sentences were read verbatim: 'This single-center, prospective, double-masked, placebo-controlled Phase II study randomized 72 qualifying subjects 1:1 to receive either [the study solution] or placebo treatment for a total of 28 days' and 'Neither of the primary endpoints, ie, ocular discomfort or inferior corneal staining, showed a significant difference between treatment and control groups at visit 5'. Caveat found on that verification and repeated here so no one is misled by the machine record: the Crossref deposit for this DOI lists a spurious first author, 'Mclaughlin, James', who does not appear on the paper. PubMed is authoritative and the author list above is correct. The formulation strength has been elided from the quoted passage and omitted from the finding, so that no concentration figure of any kind appears in this dossier. The abstract's secondary-outcome sentence and its adverse-event sentence are deliberately not reported, per this dossier's safety-framing standard.

2. Studied for

   What the whole thymosin beta-4 / TB-500 literature adds up to (2026 scoping review)

   A 2026 scoping review set out to map, rather than judge, every study on thymosin beta-4 and TB-500 in tissue healing and musculoskeletal repair. Searching PubMed, Europe PMC and ClinicalTrials.gov through March 2026, the authors screened 1,772 records and included 80 studies. Their conclusions are sobering and worth stating plainly: the literature leans heavily on dish-based and mixed designs; most of it studies thymosin beta-4 itself rather than TB-500; the best-covered tissues are skin and soft tissue, blood vessels, the eye and bone, while tendon, ligament, muscle, cartilage and spine are comparatively thin; human evidence clusters in eye and skin settings; and direct TB-500 evidence was limited to a single included study out of 80. The authors describe the mapped literature as unevenly distributed and largely preclinical. a scoping review of laboratory, animal, human and registered-trial sources, 80 studies included, by authors unrelated to the compound's development Preclinical strong More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong. Open for the full finding and the paper it came from.

   In the literature

   What the whole thymosin beta-4 / TB-500 literature adds up to (2026 scoping review)

   A 2026 scoping review set out to map, rather than judge, every study on thymosin beta-4 and TB-500 in tissue healing and musculoskeletal repair. Searching PubMed, Europe PMC and ClinicalTrials.gov through March 2026, the authors screened 1,772 records and included 80 studies. Their conclusions are sobering and worth stating plainly: the literature leans heavily on dish-based and mixed designs; most of it studies thymosin beta-4 itself rather than TB-500; the best-covered tissues are skin and soft tissue, blood vessels, the eye and bone, while tendon, ligament, muscle, cartilage and spine are comparatively thin; human evidence clusters in eye and skin settings; and direct TB-500 evidence was limited to a single included study out of 80. The authors describe the mapped literature as unevenly distributed and largely preclinical.^{References 2}

   Modela scoping review of laboratory, animal, human and registered-trial sources, 80 studies included, by authors unrelated to the compound's development

   Confidence: strong

   More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong.

   Source

   McGuire F, Hughes E, Maak T, Cushman DM. Thymosin Beta-4 and TB-500 in Tissue Healing, Regeneration, and Musculoskeletal Repair: A Scoping Review. Appl Sci. 2026;16(12):6202. doi:10.3390/app16126202

   Source

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.3390/app16126202 returned this exact title with exactly these 4 authors, McGuire Flynn, Hughes Emma, Maak Travis and Cushman Daniel M., Applied Sciences, volume 16, issue 12, article number 6202, issued 2026-06-19, type journal-article, ISSN 2076-3417. The full deposited abstract was retrieved and read on the same record; it states verbatim 'PubMed, Europe PMC, and ClinicalTrials.gov were searched through March 2026', 'Of 1772 records identified, 80 studies were included', 'most studies evaluated TB4 rather than TB-500', the tissue-category ranking, 'Human evidence was concentrated in ocular/cornea and wound/skin/soft tissue settings, whereas direct TB-500 evidence was limited to a single included study', and that the literature 'remains unevenly distributed and largely preclinical'. This paper carries no PubMed record, so Crossref is the whole of its machine verification; that is a real limit of this citation and is why it is stated here rather than implied. It is a scoping review both by title and by self-description, and is distinct from the 2025 BPC-157 review below.

3. Studied for

   How little human data exists on BPC-157 (2025 review)

   A 2025 review in a musculoskeletal medicine journal assessed how much and how good the evidence for BPC-157 really is. It credits the preclinical picture: regenerative effects across many animal models, acting through overlapping pathways including VEGFR2 and nitric oxide production via the Akt-eNOS route, plus ERK1/2 signaling. Then it states the part that matters most to anyone reading this page: human data are extremely limited, with only 3 pilot studies ever conducted in people, and rigorous large-scale trials are lacking. The authors conclude that until well-designed clinical trials are done, BPC-157 should be considered investigational, and its use approached with caution. a review of the preclinical animal, cell and limited human pilot literature, by authors unrelated to the compound's development Preclinical strong More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong. Open for the full finding and the paper it came from.

   In the literature

   How little human data exists on BPC-157 (2025 review)

   A 2025 review in a musculoskeletal medicine journal assessed how much and how good the evidence for BPC-157 really is. It credits the preclinical picture: regenerative effects across many animal models, acting through overlapping pathways including VEGFR2 and nitric oxide production via the Akt-eNOS route, plus ERK1/2 signaling. Then it states the part that matters most to anyone reading this page: human data are extremely limited, with only 3 pilot studies ever conducted in people, and rigorous large-scale trials are lacking. The authors conclude that until well-designed clinical trials are done, BPC-157 should be considered investigational, and its use approached with caution.^{References 3}

   Modela review of the preclinical animal, cell and limited human pilot literature, by authors unrelated to the compound's development

   Confidence: strong

   More than 1 independent study pointing the same way, or a controlled human trial. Read it as how well a question was studied, never as how well the material worked: the only controlled human trial on this page missed both of its primary endpoints and is still rated strong.

   Source

   McGuire FP, Martinez R, Lenz A, Skinner L, Cushman DM. Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing. Curr Rev Musculoskelet Med. 2025;18(12):611-619. doi:10.1007/s12178-025-09990-7. PMID: 40789979

   PubMed 40789979

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1007/s12178-025-09990-7 returned this exact title with exactly these 5 authors, McGuire Flynn P., Martinez Riley, Lenz Annika, Skinner Lee and Cushman Daniel M., Current Reviews in Musculoskeletal Medicine, volume 18, issue 12, pages 611-619. PubMed efetch for PMID 40789979 returned Curr Rev Musculoskelet Med. 2025 Dec;18(12):611-619, Epub 2025 Aug 12, PMCID PMC12446177, University of Utah affiliations, a declared absence of competing interests, and the structured abstract, which states verbatim 'rigorous, large-scale trials are lacking' and 'BPC-157 should be considered investigational, and its use approached with caution'. NAMING AMBIGUITY, carried forward rather than smoothed over: this paper is titled a narrative review but its own abstract opens 'This scoping review aims to evaluate', and it sits beside reference 2, an actual scoping review by overlapping authors at the same institution. The 2 are separated here by year and by compound in their area titles so they cannot be confused for each other. The abstract's own list of the 3 pilot indications is deliberately not restated, and its adverse-event sentence is deliberately not reported, per this dossier's safety-framing standard. An earlier draft attributed this paper to 'Kraus J et al. (eds.)', which both Crossref and PubMed contradict; that correction stays applied.

4. Studied for

   Healing of a cut Achilles tendon in living rats (BPC-157)

   In rats whose right Achilles tendon was cut through, leaving a visible gap between the 2 ends, animals given BPC-157 recovered better than saline controls on every measure the study used: the tendon took more load before failing and was stiffer, the animals walked better on a standard footprint score, the tissue under the microscope showed better-formed repair tissue, and the visible gap was smaller and eventually closed. In the same paper's dish experiments, BPC-157 on its own did not make cultured tendon cells grow at all; what it did was reverse the growth-blocking effect of 4-hydroxynonenal, a damaging breakdown product, in those cultures. IN VITRO RODENT rodent (rat Achilles tendon transection) plus in vitro (cultured rat tendon cells) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Healing of a cut Achilles tendon in living rats (BPC-157)

   In rats whose right Achilles tendon was cut through, leaving a visible gap between the 2 ends, animals given BPC-157 recovered better than saline controls on every measure the study used: the tendon took more load before failing and was stiffer, the animals walked better on a standard footprint score, the tissue under the microscope showed better-formed repair tissue, and the visible gap was smaller and eventually closed. In the same paper's dish experiments, BPC-157 on its own did not make cultured tendon cells grow at all; what it did was reverse the growth-blocking effect of 4-hydroxynonenal, a damaging breakdown product, in those cultures.^{References 4}

   Modelrodent (rat Achilles tendon transection) plus in vitro (cultured rat tendon cells)

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Staresinic M, Sebecic B, Patrlj L, et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res. 2003;21(6):976-983. doi:10.1016/S0736-0266(03)00110-4. PMID: 14554208

   PubMed 14554208

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1016/S0736-0266(03)00110-4 returned this exact title, first author Staresinic M., then Sebecic B and Patrlj L, Journal of Orthopaedic Research, volume 21, issue 6, pages 976-983, issued 2003-11. PubMed efetch for PMID 14554208 returned J Orthop Res. 2003 Nov;21(6):976-83 and the full abstract, from which the surgical model and the biomechanical, functional, microscopic and macroscopic outcomes were read. CORRECTED FINDING, kept visible because it is the defect class this corpus watches for: the abstract's own wording on the cell-culture arm is that BPC 157 presents 'with no effect on the growth of cultured cell of its own' and reverses the growth-inhibiting effect of 4-hydroxynonenal. An earlier draft claimed the paper showed in vitro stimulation of tendocyte growth, language lifted from the paper's title and contradicted by its own abstract. The finding above says what the abstract says, not what the title says. Dose and frequency figures present in the abstract are deliberately omitted. This is 1 of the 4 entries from the University of Zagreb group disclosed in the background section above.

5. Studied for

   Tendon reattaching to bone, and the effect of a corticosteroid (BPC-157)

   Rats had the Achilles tendon cleanly detached from the heel bone, an injury the authors state does not heal back on its own. Over 3 weeks, animals given BPC-157 walked better on the standard footprint score, and the repaired junction took more load before failing and was stiffer. Under the microscope the collagen fibers were better organized, there was more type I collagen, and the new blood supply was further along. A corticosteroid drug, 6-alpha-methylprednisolone, consistently made healing worse in this model, and the paper reports that BPC-157 substantially reduced that harm. Read that wording carefully: reduced, not abolished. RODENT rodent (rat Achilles tendon-to-bone detachment) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Tendon reattaching to bone, and the effect of a corticosteroid (BPC-157)

   Rats had the Achilles tendon cleanly detached from the heel bone, an injury the authors state does not heal back on its own. Over 3 weeks, animals given BPC-157 walked better on the standard footprint score, and the repaired junction took more load before failing and was stiffer. Under the microscope the collagen fibers were better organized, there was more type I collagen, and the new blood supply was further along. A corticosteroid drug, 6-alpha-methylprednisolone, consistently made healing worse in this model, and the paper reports that BPC-157 substantially reduced that harm. Read that wording carefully: reduced, not abolished.^{References 5}

   Modelrodent (rat Achilles tendon-to-bone detachment)

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res. 2006;24(5):982-989. doi:10.1002/jor.20096. PMID: 16583442

   PubMed 16583442

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1002/jor.20096 returned this exact title with exactly these 5 authors, Krivic Andrija, Anic Tomislav, Seiwerth Sven, Huljev Dubravko and Sikiric Predrag, Journal of Orthopaedic Research, volume 24, issue 5, pages 982-989, 2006. PubMed efetch for PMID 16583442 returned J Orthop Res. 2006 May;24(5):982-9 with the identical author list and the abstract, which states 'tendon to bone could not be healed spontaneously', lists the functional (Achilles functional index), biomechanical (load to failure, stiffness, Young elasticity modulus) and immunohistochemical (collagen fiber organization, collagen type I, advanced vascular appearance) outcomes, and states verbatim that '6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation'. The verb 'reduces' is deliberately not upgraded. Dose figures in the abstract are deliberately omitted. This is 1 of the 4 University of Zagreb entries disclosed above.

6. Studied for

   Blood vessel growth and VEGFR2 signaling (BPC-157)

   One study tested BPC-157 for effects on new blood vessel growth in several systems at once. On the membrane of a developing chick egg, which is living tissue, and in a dish-based vessel-forming assay, vessel density went up. In rats whose hind-limb blood supply had been cut off, blood flow came back faster on laser scanning, and the muscle tissue afterward contained more vessels and showed more of the receptor VEGFR2 on them. In cultured human blood-vessel lining cells, BPC-157 raised VEGFR2 itself but not its usual trigger VEGF-A, pulled VEGFR2 inside the cell, and switched on the VEGFR2-Akt-eNOS chain over time. Blocking the pulling-inside step with a chemical called dynasore shut all of that down, which is what tied the effect to that specific receptor step. IN VITRO RODENT AVIAN IN VIVO chick chorioallantoic membrane (avian in vivo), rodent (rat hind-limb ischemia), and in vitro (cultured human vascular endothelial cells) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Blood vessel growth and VEGFR2 signaling (BPC-157)

   One study tested BPC-157 for effects on new blood vessel growth in several systems at once. On the membrane of a developing chick egg, which is living tissue, and in a dish-based vessel-forming assay, vessel density went up. In rats whose hind-limb blood supply had been cut off, blood flow came back faster on laser scanning, and the muscle tissue afterward contained more vessels and showed more of the receptor VEGFR2 on them. In cultured human blood-vessel lining cells, BPC-157 raised VEGFR2 itself but not its usual trigger VEGF-A, pulled VEGFR2 inside the cell, and switched on the VEGFR2-Akt-eNOS chain over time. Blocking the pulling-inside step with a chemical called dynasore shut all of that down, which is what tied the effect to that specific receptor step.^{References 6}

   Modelchick chorioallantoic membrane (avian in vivo), rodent (rat hind-limb ischemia), and in vitro (cultured human vascular endothelial cells)

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Hsieh MJ, Liu HT, Wang CN, et al. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl). 2017;95(3):323-333. doi:10.1007/s00109-016-1488-y. PMID: 27847966

   PubMed 27847966

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1007/s00109-016-1488-y returned this exact title, first author Hsieh Ming-Jer, then Liu Hsien-Ta and Wang Chao-Nin, Journal of Molecular Medicine, volume 95, issue 3, pages 323-333. PubMed efetch for PMID 27847966 returned J Mol Med (Berl). 2017 Mar;95(3):323-333, Epub 2016 Nov 15, and the abstract, which states verbatim 'As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively', so the CAM assay is the in vivo arm and the model field above places it there. CORRECTED MODEL ATTRIBUTION, carried forward: an earlier draft filed the CAM assay under in vitro. The abstract also states the rat hind-limb laser Doppler result, 'increased mRNA and protein expressions of VEGFR2 but not VEGF-A', dynasore-blocked internalization, and time-dependent VEGFR2-Akt-eNOS activation. Affiliation on the record is Chang Gung University, Taiwan, independent of the University of Zagreb group. Confidence is held at moderate under this dossier's own rubric: a single study, however many systems it ran.

7. Studied for

   Skin healing after a chemical burn (BPC-157)

   Rats were given an alkali burn to the skin. Where BPC-157 was applied to the wound, the wound closed faster, and stained sections of skin taken 18 days later showed more repair tissue, more new surface skin, more remodeling of the deeper layer and more collagen than in the model control group. The burned tissue also carried more of the vessel-growth signal VEGF. In parallel dish experiments on human blood-vessel lining cells, the peptide increased how fast the cells multiplied and how far they migrated in 2 different assays, sped up the formation of vessel-like tubes, and altered ERK1/2 signaling along with its downstream targets c-Fos, c-Jun and Egr-1. IN VITRO RODENT rodent (rat alkali-burn skin wound, topical application) plus in vitro (human umbilical vein endothelial cells) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Skin healing after a chemical burn (BPC-157)

   Rats were given an alkali burn to the skin. Where BPC-157 was applied to the wound, the wound closed faster, and stained sections of skin taken 18 days later showed more repair tissue, more new surface skin, more remodeling of the deeper layer and more collagen than in the model control group. The burned tissue also carried more of the vessel-growth signal VEGF. In parallel dish experiments on human blood-vessel lining cells, the peptide increased how fast the cells multiplied and how far they migrated in 2 different assays, sped up the formation of vessel-like tubes, and altered ERK1/2 signaling along with its downstream targets c-Fos, c-Jun and Egr-1.^{References 7}

   Modelrodent (rat alkali-burn skin wound, topical application) plus in vitro (human umbilical vein endothelial cells)

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Huang T, Zhang K, Sun L, et al. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug Des Devel Ther. 2015;9:2485-2499. doi:10.2147/DDDT.S82030. PMID: 25995620

   PubMed 25995620

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.2147/DDDT.S82030 returned this exact title, Drug Design, Development and Therapy, 2015, first page 2485. PubMed efetch for PMID 25995620 returned Drug Des Devel Ther. 2015 Apr 30;9:2485-99, PMCID PMC4425239, with author order Huang T, Zhang K, Sun L, Xue X, Zhang C, Shu Z, Mu N, Gu J and others, matching the citation as written. Noted for the record: Crossref's deposited author order for this DOI differs from MEDLINE's, listing Gu J third; the PubMed and MEDLINE order is used here. The abstract states the alkali burn rat model, the day-18 hematoxylin-eosin and Masson staining results, the VEGF result in wounded skin, and the HUVEC proliferation, transwell and wound-healing migration, tube formation and ERK1/2, c-Fos, c-Jun and Egr-1 findings as written above. Affiliation is the Fourth Military Medical University, Xi'an, independent of the University of Zagreb and Chang Gung groups. The finding is specific to topical application in this model and says nothing about any other route.

8. Studied for

   Healing of a gap cut out of bone (BPC-157)

   A segment was removed from the middle of 1 forearm bone in rabbits, leaving a gap that in every saline control animal was still not healed 6 weeks later. Against that baseline, BPC-157 significantly improved healing. On x-ray callus measurement, bone-density imaging and quantitative tissue measurement, certain BPC-157 regimens produced improvement on a par with the 2 standard comparisons the study ran: packing the gap with the animal's own bone marrow, or filling it with a graft of its own cortical bone. More of the animals given BPC-157 ended up with bone running continuously across the gap. The authors state the finding requires further investigation. rabbit (segmental radial bone defect) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Healing of a gap cut out of bone (BPC-157)

   A segment was removed from the middle of 1 forearm bone in rabbits, leaving a gap that in every saline control animal was still not healed 6 weeks later. Against that baseline, BPC-157 significantly improved healing. On x-ray callus measurement, bone-density imaging and quantitative tissue measurement, certain BPC-157 regimens produced improvement on a par with the 2 standard comparisons the study ran: packing the gap with the animal's own bone marrow, or filling it with a graft of its own cortical bone. More of the animals given BPC-157 ended up with bone running continuously across the gap. The authors state the finding requires further investigation.^{References 8}

   Modelrabbit (segmental radial bone defect)

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Sebecic B, Nikolic V, Sikiric P, et al. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. Bone. 1999;24(3):195-202. doi:10.1016/S8756-3282(98)00180-X. PMID: 10071911

   PubMed 10071911

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1016/S8756-3282(98)00180-X returned this exact title, first author Sebecic B, then Nikolic V and Sikiric P, journal Bone, volume 24, issue 3, pages 195-202, issued 1999-03. PubMed efetch for PMID 10071911 returned Bone. 1999 Mar;24(3):195-202 with the same author order and the full abstract, which describes 'a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks', the bone marrow and autologous cortical graft comparators, that 'Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects', the callus surface, microphotodensitometry and quantitative histomorphometry readouts, the increased number of animals with 'complete bony continuity across the defect site', and the closing statement that the effect 'requires further investigation'. The abstract's dose figures are deliberately omitted. This is the only rabbit study on this page, and it is 1 of the 4 University of Zagreb entries disclosed above.

9. Studied for

   Protection of tissue and rerouting of blood flow (BPC-157, review by the originating group)

   A 2020 review positions BPC-157 as a likely mediator of a long-standing idea in gastroenterology called Robert's cytoprotection: the observation that the stomach lining can be protected against damaging agents. It gathers preclinical work in which BPC-157 kept the stomach lining intact against harmful agents, protected the lining of blood vessels, and produced what the authors describe as vessel recruitment, meaning blood re-routes around a blocked vessel through additional shunts and bypass loops. Those models include ischemia and reperfusion in the bowel, duodenal lesions, cecal perforation and occlusion of the inferior vena cava. This citation supports the tissue-protection and vessel-rerouting claims only; the VEGFR2 mechanism above is supported by Hsieh 2017, not by this review. a narrative review of rat and cell studies, written by the University of Zagreb group that first described the peptide Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

   In the literature

   Protection of tissue and rerouting of blood flow (BPC-157, review by the originating group)

   A 2020 review positions BPC-157 as a likely mediator of a long-standing idea in gastroenterology called Robert's cytoprotection: the observation that the stomach lining can be protected against damaging agents. It gathers preclinical work in which BPC-157 kept the stomach lining intact against harmful agents, protected the lining of blood vessels, and produced what the authors describe as vessel recruitment, meaning blood re-routes around a blocked vessel through additional shunts and bypass loops. Those models include ischemia and reperfusion in the bowel, duodenal lesions, cecal perforation and occlusion of the inferior vena cava. This citation supports the tissue-protection and vessel-rerouting claims only; the VEGFR2 mechanism above is supported by Hsieh 2017, not by this review.^{References 9}

   Modela narrative review of rat and cell studies, written by the University of Zagreb group that first described the peptide

   Confidence: moderate

   A single solid preclinical study in a living animal. One laboratory, one design, one species.

   Source

   Sikiric P, Hahm KB, Blagaic AB, et al. Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future. Gut Liver. 2020;14(2):153-167. doi:10.5009/gnl18490. PMID: 31158953

   PubMed 31158953

   How this citation was checked

   Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.5009/gnl18490 returned this exact title, first author Sikiric Predrag, then Hahm Ki-Baik and Blagaic Alenka Boban, Gut and Liver, volume 14, issue 2, pages 153-167, issued 2020-03-15. PubMed efetch for PMID 31158953 returned Gut Liver. 2020 Mar 15;14(2):153-167, PMCID PMC7096228, plus the abstract, read in full: it states the gastric-integrity protection, the generalization of gastric endothelial protection to other vessels, and the 'vessel recruitment that circumvents vessel occlusion and the development of additional shunting and rapid bypass loops' with the named models. The abstract contains no mention of VEGFR2, receptor internalization or eNOS, which is why that mechanism is attributed to Hsieh 2017 instead and not to this review. REASSIGNED CLAIM, carried forward: an earlier draft attributed the VEGFR2 and eNOS mechanism here. Author affiliations on the same record confirm the University of Zagreb attribution above, and this is the 4th and last of those entries. The abstract's cachexia and muscle-wasting signaling content is deliberately not reported here; verification.omitted_claims records why. Confidence is capped at moderate under this dossier's rubric, which holds a review down 1 level when the reviewing authors are the group that first described the compound.

10. Studied for

    Closure of an open skin wound and movement of skin cells (thymosin beta-4)

    In rats with a full-thickness skin wound, thymosin beta-4 was applied either onto the wound or delivered into the abdominal cavity. New surface skin covered the wound 42% more than in saline controls at 4 days, and by as much as 61% at 7 days. Those wounds also pulled closed at least 11% more than controls by day 7, and showed more collagen and more new blood vessels. In a separate dish test, the peptide made skin cells migrate 2 to 3 times more than medium alone within 4 to 5 hours. IN VITRO RODENT rodent (rat full-thickness skin wound) plus in vitro (skin-cell migration assay) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

    In the literature

    Closure of an open skin wound and movement of skin cells (thymosin beta-4)

    In rats with a full-thickness skin wound, thymosin beta-4 was applied either onto the wound or delivered into the abdominal cavity. New surface skin covered the wound 42% more than in saline controls at 4 days, and by as much as 61% at 7 days. Those wounds also pulled closed at least 11% more than controls by day 7, and showed more collagen and more new blood vessels. In a separate dish test, the peptide made skin cells migrate 2 to 3 times more than medium alone within 4 to 5 hours.^{References 10}

    Modelrodent (rat full-thickness skin wound) plus in vitro (skin-cell migration assay)

    Confidence: moderate

    A single solid preclinical study in a living animal. One laboratory, one design, one species.

    Source

    Malinda KM, Sidhu GS, Mani H, Banaudha K, Maheshwari RK, Goldstein AL, Kleinman HK. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368. doi:10.1046/j.1523-1747.1999.00708.x. PMID: 10469335

    PubMed 10469335

    How this citation was checked

    Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1046/j.1523-1747.1999.00708.x returned the title 'Thymosin beta4 Accelerates Wound Healing', first author Malinda Katherine M., Journal of Investigative Dermatology, volume 113, issue 3, pages 364-368, issued 1999-09. PubMed efetch for PMID 10469335 returned J Invest Dermatol. 1999 Sep;113(3):364-8 with the author order used in the citation above and the abstract, which states verbatim 'increased reepithelialization by 42% over saline controls at 4 d and by as much as 61% at 7 d post-wounding', 'contracted at least 11% more than controls by day 7', and 'migration was stimulated 2-3-fold over migration with medium alone'. Noted for the record: Crossref's deposited author order for this DOI differs from MEDLINE's, listing Kleinman second; the PubMed and MEDLINE order is used here. DROPPED CITATION, carried forward: an earlier draft cited this finding to 'Malinda KM et al., FASEB J, 1999;13(13):1775-1783, doi:10.1096/fasebj.13.13.1775', a DOI that returns HTTP 404 from Crossref. The science was sound, so the finding was re-cited to the paper that actually reports it, which is this one. This paper shares its investigating authors (Goldstein and Kleinman) with reference 14, which is why neither counts as independent corroboration of the other.

11. Studied for

    Cell migration and survival in an injured heart (thymosin beta-4)

    Thymosin beta-4 made heart muscle cells and vessel-lining cells move in the developing embryonic heart, and kept that effect in heart cells after birth. Heart cells in culture also survived better with it. The study found the peptide latches onto 2 partner proteins, PINCH and integrin-linked kinase, which turns on the survival switch Akt. In mice whose coronary artery was tied off, thymosin beta-4 raised integrin-linked kinase and Akt activity in the heart, more heart muscle cells survived early on, and heart function was better. It is included here because an independent group corroborates the migration-and-survival signaling role of the peptide. It is a heart injury model and says nothing about tendon, muscle or skin. IN VITRO RODENT rodent (mouse coronary artery ligation) plus in vitro (cultured embryonic and newborn heart cells) Preclinical moderate A single solid preclinical study in a living animal. One laboratory, one design, one species. Open for the full finding and the paper it came from.

    In the literature

    Cell migration and survival in an injured heart (thymosin beta-4)

    Thymosin beta-4 made heart muscle cells and vessel-lining cells move in the developing embryonic heart, and kept that effect in heart cells after birth. Heart cells in culture also survived better with it. The study found the peptide latches onto 2 partner proteins, PINCH and integrin-linked kinase, which turns on the survival switch Akt. In mice whose coronary artery was tied off, thymosin beta-4 raised integrin-linked kinase and Akt activity in the heart, more heart muscle cells survived early on, and heart function was better. It is included here because an independent group corroborates the migration-and-survival signaling role of the peptide. It is a heart injury model and says nothing about tendon, muscle or skin.^{References 11}

    Modelrodent (mouse coronary artery ligation) plus in vitro (cultured embryonic and newborn heart cells)

    Confidence: moderate

    A single solid preclinical study in a living animal. One laboratory, one design, one species.

    Source

    Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466-472. doi:10.1038/nature03000. PMID: 15565145

    PubMed 15565145

    How this citation was checked

    Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1038/nature03000 returned this exact title, first author Bock-Marquette Ildiko, with Saxena Ankur, White Michael D., DiMaio J. Michael and Srivastava Deepak, Nature, volume 432, issue 7016, pages 466-472, issued 2004-11. PubMed efetch for PMID 15565145 returned Nature. 2004 Nov 25;432(7016):466-72 with the same authors and the abstract, which states that 'the G-actin sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes', that survival in culture 'was also enhanced', that the peptide 'formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt', and that 'After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function'. Affiliation on the record is UT Southwestern, unrelated to the thymosin beta-4 originating group, which is what supports the independence claim in the finding. This abstract is also the independent corroboration for the actin-sequestering description in reference 13. The paper reports no scar, infarct-size or remodeling measurement, and none is claimed here.

12. Studied for

    Tendon cell outgrowth, survival and migration in culture (BPC-157)

    Researchers took small pieces of rat Achilles tendon and grew them in dishes, along with tendon cells isolated from the same tendon. With BPC-157 in the culture, cells grew out of the tendon pieces faster, and more of them survived when the dish was stressed with hydrogen peroxide. The cells also moved further and spread out more, and did so more strongly at higher concentrations. Two proteins involved in how a cell grips its surroundings and pulls itself along, FAK and paxillin, were switched on in step with that. Notably, the peptide did not make the cells multiply faster in the standard proliferation test. This study did not itself cut any tendon in a living animal; the cut-tendon model is mentioned in its introduction as earlier work by others. IN VITRO EX VIVO in vitro and ex vivo (cultured rat Achilles tendon fibroblasts and tendon explants) Preclinical preliminary Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too. Open for the full finding and the paper it came from.

    In the literature

    Tendon cell outgrowth, survival and migration in culture (BPC-157)

    Researchers took small pieces of rat Achilles tendon and grew them in dishes, along with tendon cells isolated from the same tendon. With BPC-157 in the culture, cells grew out of the tendon pieces faster, and more of them survived when the dish was stressed with hydrogen peroxide. The cells also moved further and spread out more, and did so more strongly at higher concentrations. Two proteins involved in how a cell grips its surroundings and pulls itself along, FAK and paxillin, were switched on in step with that. Notably, the peptide did not make the cells multiply faster in the standard proliferation test. This study did not itself cut any tendon in a living animal; the cut-tendon model is mentioned in its introduction as earlier work by others.^{References 12}

    Modelin vitro and ex vivo (cultured rat Achilles tendon fibroblasts and tendon explants)

    Confidence: preliminary

    Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too.

    Source

    Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011;110(3):774-780. doi:10.1152/japplphysiol.00945.2010. PMID: 21030672

    PubMed 21030672

    How this citation was checked

    Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1152/japplphysiol.00945.2010 returned this exact title, first author Chang Chung-Hsun, with Tsai Wen-Chung, Lin Miao-Sui, Hsu Ya-Hui and Pang Jong-Hwei Su, Journal of Applied Physiology, volume 110, issue 3, pages 774-780, issued 2011-03. PubMed efetch for PMID 21030672 returned J Appl Physiol (1985). 2011 Mar;110(3):774-80, Epub 2010 Oct 28, same author list, plus the full abstract, which states that BPC 157 'significantly accelerated the outgrowth of tendon explants', that proliferation 'was not directly affected by BPC 157 as evaluated by MTT assay', that survival 'was significantly increased under the H(2)O(2) stress', that migration increased 'in a dose-dependent manner as revealed by transwell filter migration assay', and that 'the phosphorylation levels of both FAK and paxillin were dose dependently increased'. CORRECTED MODEL, carried forward: an earlier draft framed this as a rat Achilles tendon transection model. The abstract's only mention of a transected tendon is as prior background by others, so no attribution of that prior work is made here and confidence is held at preliminary. The concentration-dependence wording above drops the source abstract's own term, which is on the store-wide banned list; the increases the study reported are still stated. Affiliation is Chang Gung University, Taiwan, independent of the University of Zagreb group.

13. Studied for

    What thymosin beta-4 actually does to actin, the cell's scaffolding protein

    Cells build their internal scaffolding out of a protein called actin, and they keep a large pool of it in loose, unassembled form so it is ready when needed. In resting human platelets, most of that loose actin was found bound to a small peptide the authors had called Fx. This paper showed that Fx and thymosin beta-4 are the same molecule: the complete amino acid sequence of Fx turned out to be identical to thymosin beta-4, and authentic thymosin beta-4 behaved identically, binding actin one-to-one and blocking it from assembling. This is the biochemical basis for the standard description of thymosin beta-4 as an actin-sequestering peptide, a description carried forward independently in later work by unrelated groups. IN VITRO in vitro (purified protein: peptide and actin isolated from human platelets and muscle) Preclinical preliminary Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too. Open for the full finding and the paper it came from.

    In the literature

    What thymosin beta-4 actually does to actin, the cell's scaffolding protein

    Cells build their internal scaffolding out of a protein called actin, and they keep a large pool of it in loose, unassembled form so it is ready when needed. In resting human platelets, most of that loose actin was found bound to a small peptide the authors had called Fx. This paper showed that Fx and thymosin beta-4 are the same molecule: the complete amino acid sequence of Fx turned out to be identical to thymosin beta-4, and authentic thymosin beta-4 behaved identically, binding actin one-to-one and blocking it from assembling. This is the biochemical basis for the standard description of thymosin beta-4 as an actin-sequestering peptide, a description carried forward independently in later work by unrelated groups.^{References 13}

    Modelin vitro (purified protein: peptide and actin isolated from human platelets and muscle)

    Confidence: preliminary

    Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too.

    Source

    Safer D, Elzinga M, Nachmias VT. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem. 1991;266(7):4029-4032. doi:10.1016/S0021-9258(20)64278-8. PMID: 1999398

    PubMed 1999398

    How this citation was checked

    Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1016/S0021-9258(20)64278-8 returned the title 'Thymosin beta4 and Fx, an actin-sequestering peptide, are indistinguishable' with exactly these 3 authors, Safer D, Elzinga M and Nachmias V T, Journal of Biological Chemistry, volume 266, issue 7, pages 4029-4032, issued 1991-03. PubMed efetch for PMID 1999398 returned J Biol Chem. 1991 Mar 5;266(7):4029-32 with the same authors and the abstract, which states that purified Fx 'binds stoichiometrically to muscle G-actin', that 'formation of the complex inhibits salt-induced polymerization of G-actin', that the complete amino acid sequence of Fx 'was found to be identical with that of thymosin beta 4', and that authentic thymosin beta 4 forms 'a 1:1 complex with actin monomers and inhibiting polymerization'. CORRECTED CONFIDENCE, carried forward: this entry was once labeled moderate. It is purified-protein biochemistry from a single study, which this dossier's rubric puts at preliminary, and it is relabeled to match. The independent corroboration named in the finding is reference 11, whose abstract refers to 'the G-actin sequestering peptide thymosin beta4'.

14. Studied for

    Wound repair and vessel growth in old animals (thymosin beta-4)

    A short 2004 summary paper by the investigating group reports that thymosin beta-4 promotes new blood vessel growth and wound repair in rodents that are old as well as rodents that are young. The starting observation is that aged animals grow fewer new vessels and heal badly. The authors state the peptide works by increasing vessel growth and cell movement, and note that it was in clinical trials for wound repair at the time of writing in 2004. This is a 3-page summary of the group's own work, not a new experiment, which is why it is graded low and why nothing in it should be read as an independent result. a short summary review of the authors' own rat work; no new data reported Preclinical preliminary Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too. Open for the full finding and the paper it came from.

    In the literature

    Wound repair and vessel growth in old animals (thymosin beta-4)

    A short 2004 summary paper by the investigating group reports that thymosin beta-4 promotes new blood vessel growth and wound repair in rodents that are old as well as rodents that are young. The starting observation is that aged animals grow fewer new vessels and heal badly. The authors state the peptide works by increasing vessel growth and cell movement, and note that it was in clinical trials for wound repair at the time of writing in 2004. This is a 3-page summary of the group's own work, not a new experiment, which is why it is graded low and why nothing in it should be read as an independent result.^{References 14}

    Modela short summary review of the authors' own rat work; no new data reported

    Confidence: preliminary

    Cell-culture or isolated-tissue work only, or a single small study. A review that reports no new data of its own sits here too.

    Source

    Philp D, Goldstein AL, Kleinman HK. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev. 2004;125(2):113-115. doi:10.1016/j.mad.2003.11.005. PMID: 15037013

    PubMed 15037013

    How this citation was checked

    Verified in the research pass on 2026-07-28 and carried forward unchanged. Crossref GET /works/10.1016/j.mad.2003.11.005 returned this exact title with exactly these 3 authors, Philp D., Goldstein A.L. and Kleinman H.K., Mechanisms of Ageing and Development, volume 125, issue 2, pages 113-115, issued 2004-02. PubMed efetch for PMID 15037013 returned Mech Ageing Dev. 2004 Feb;125(2):113-5 and the whole abstract, which states 'In aged animals, angiogenesis is reduced resulting in poor wound healing', that thymosin beta(4) 'promotes angiogenesis and wound repair in both normal and aged rodents', that 'It acts by increasing angiogenesis and cell migration' and that it 'is currently in clinical trials for wound repair'. Three pages total, no new data. DROPPED CITATION, carried forward: an earlier draft carried 'Grant DS et al., Ann N Y Acad Sci, 2004' for this finding, a record that resolves in neither Crossref nor PubMed; it was replaced with this paper, which actually states it. CORRECTED CONFIDENCE, carried forward: once labeled moderate, relabeled preliminary to match this dossier's rubric for a summary review with no new data by the investigating group. The hair-follicle content named in the title is deliberately not reported in the finding; verification.omitted_claims records why. This paper shares its investigating authors with reference 10.

3 strong / 8 moderate / 3 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.