ArticleActa biomaterialia2014
Enhanced trophic factor secretion by mesenchymal stem/stromal cells with Glycine-Histidine-Lysine (GHK)-modified alginate hydrogels.
Article in Acta biomaterialia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 74 citations in OpenAlex.
- A Systematic Review of the Mechanisms and Therapeutic Applications of GHK-Cu (Glycyl-L-Histidyl-L-Lysine-Copper Complex) in Topical Microneedle Delivery: A Case for Expanded Clinical Trials.Archives of internal medicine research · 2026Article
- Edible Sulfonated Soy Protein Microcarriers for Cultivated Meat Cell Expansion.Journal of biomedical materials research. Part A · 2026Article
- Protective Functions of β-Alanyl-L-Histidine and Glycyl-L-Histidyl-L-Lysine Glycoconjugates and Copper in Concert.Antioxidants (Basel, Switzerland) · 2025Review
- Advances in Transdermal Delivery Systems for Treating Androgenetic Alopecia.Pharmaceutics · 2025Review
- Nanoengineered Self-Assembling Peptides with Increased Proteolytic Stability Promote Wound Healing.ACS applied materials & interfaces · 2025Article
- The naturally occurring peptide GHK reverses age-related fibrosis by modulating myofibroblast function.Aging pathobiology and therapeutics · 2024Article
- Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.World journal of stem cells · 2024Review
- Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application.Bioactive materials · 2024Article
- Hydrogel Encapsulation: Taking the Therapy of Mesenchymal Stem Cells and Their Derived Secretome to the Next Level.Frontiers in bioengineering and biotechnology · 2022Review
- Metabolomics in Bone Research.Metabolites · 2021Review
- Bone Matrix Non-Collagenous Proteins in Tissue Engineering: Creating New Bone by Mimicking the Extracellular Matrix.Polymers · 2021Review
- Electrospun fibers enhanced the paracrine signaling of mesenchymal stem cells for cartilage regeneration.Stem cell research & therapy · 2021Article
- Effect of Pore Size on Cell Behavior Using Melt Electrowritten Scaffolds.Frontiers in bioengineering and biotechnology · 2021Article
- Multi-peptide presentation and hydrogel mechanics jointly enhance therapeutic duo-potential of entrapped stromal cells.Biomaterials · 2020Article
- 3D Bioprinting for Vascularized Tissue-Engineered Bone Fabrication.Materials (Basel, Switzerland) · 2020Review
- Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration.Stem cell research & therapy · 2020Article
- Glycine-Histidine-Lysine (GHK) Alleviates Astrocytes Injury of Intracerebral Hemorrhage via the Akt/miR-146a-3p/AQP4 Pathway.Frontiers in neuroscience · 2020Article
- Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments.Frontiers in bioengineering and biotechnology · 2020Review
- Perspective: Biophysical regulation of cancerous and normal blood cell lineages in hematopoietic malignancies.APL bioengineering · 2018Article
- Hypoxic Preconditioning of Mesenchymal Stem Cells with Subsequent Spheroid Formation Accelerates Repair of Segmental Bone Defects.Stem cells (Dayton, Ohio) · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Recombinant proteins and cytokines are under broad preclinical and clinical investigation to promote angiogenesis, but their success is limited by ineffective delivery, lack of long-term stability and excessive cost. Mesenchymal stem/stromal cells (MSC) secrete bioactive trophic factors, and thus, may provide an effective alternative to address these challenges. Glycine-Histidine-Lysine (GHK) is a peptide fragment of osteonectin, a matricellular protein with reported proangiogenic potential. We examined the capacity of GHK to up-regulate secretion of proangiogenic factors from human MSC in culture and when covalently coupled to alginate hydrogels. GHK had no apparent cytotoxic effects on MSC in culture over a wide range of concentrations. We detected a dose-dependent increase in vascular endothelial growth factor (VEGF) concentration in media conditioned by GHK-treated MSC, which increased endothelial cell proliferation, migration and tubule formation. We covalently coupled GHK to alginate using carbodiimide chemistry, and human MSC were entrapped in alginate hydrogels to assess VEGF secretion. Similar to monolayer culture, MSC responded to GHK-modified gels by secreting increased concentrations of VEGF and basic fibroblast growth factor compared to unmodified gels. The pre-treatment of MSC with antibodies to α6 and β1 integrins prior to entrapment in GHK-modified gels abrogated VEGF secretion, suggesting that the proangiogenic response of MSC was integrin-mediated. These data demonstrate that the proangiogenic potential of MSC can be significantly increased by the presentation of GHK with a biodegradable carrier, therefore increasing their clinical potential when used for tissue repair.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.