{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:25:50Z","timestamp":1781864750008,"version":"3.54.5"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["STRATEGMED1\/235077\/9\/NCBR\/2014"],"award-info":[{"award-number":["STRATEGMED1\/235077\/9\/NCBR\/2014"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today\u2019s science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name \u201cImunofan\u201d (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant (p &lt; 0.05) pro-proliferative activity (30\u201340% and 20\u201350% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations (p &lt; 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation (p &lt; 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB\/c and 36% in C57BL\/6 in comparison to control).<\/jats:p>","DOI":"10.3390\/molecules25122884","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T10:54:59Z","timestamp":1592996099000},"page":"2884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Imunofan\u2014RDKVYR Peptide\u2014Stimulates Skin Cell Proliferation and Promotes Tissue Repair"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-3202","authenticated-orcid":false,"given":"Justyna","family":"Sawicka","sequence":"first","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Chemistry, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0861-2514","authenticated-orcid":false,"given":"Maria","family":"Dzier\u017cy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Chemistry, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4392-5594","authenticated-orcid":false,"given":"Anna","family":"Wardowska","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-770X","authenticated-orcid":false,"given":"Milena","family":"Deptu\u0142a","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-4055","authenticated-orcid":false,"given":"Piotr","family":"Rogujski","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland"},{"name":"NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-0279","authenticated-orcid":false,"given":"Pawe\u0142","family":"Sosnowski","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Biotechnology, Faculty of Chemistry, Gda\u0144sk University of Technology, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-2649","authenticated-orcid":false,"given":"Natalia","family":"Filipowicz","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-416 Gda\u0144sk, Poland"},{"name":"International Research Agenda 3P-Medicine Laboratory, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9952","authenticated-orcid":false,"given":"Alina","family":"Mieczkowska","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Sass","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Biotechnology, Faculty of Chemistry, Gda\u0144sk University of Technology, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Biology, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-3263","authenticated-orcid":false,"given":"Aleksandra","family":"Ha\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Biology, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8531-7327","authenticated-orcid":false,"given":"Adriana","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Department of Embryology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Gucwa","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Karska","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Faculty of Chemistry, University of Gda\u0144sk, 80-308 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-6301","authenticated-orcid":false,"given":"Jolanta","family":"Kami\u0144ska","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Biotechnology, Faculty of Chemistry, Gda\u0144sk University of Technology, 80-233 Gda\u0144sk, 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Transl. Med."},{"key":"ref_2","first-page":"1309","article-title":"Van A Synthetic Pentapeptide with Biological Activity Characteristic of the Thymic Hormone","volume":"204","author":"Goldstein","year":"1979","journal-title":"Source Sci. New Ser."},{"key":"ref_3","first-page":"173","article-title":"Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth","volume":"20","author":"Barak","year":"1992","journal-title":"Exp. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.regpep.2012.11.004","article-title":"Thymohexin exhibits cytoprotective effect in experimental gastric lesions in rats both through the inhibition of inducible nitric oxide synthase and reduction of oxidative mucosal damage","volume":"180","author":"Nasadyuk","year":"2013","journal-title":"Regul. Pept."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1155\/S0962935196000592","article-title":"Changes in TNF and IL-6 production after diphtheria toxoid vaccination: Drug modulation of the cytokine levels","volume":"5","author":"Pukhalsky","year":"1996","journal-title":"Mediators Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bobrysheva, I., and Kashchenko, S. (2013, January 30). Ultrastructural changes of thyrotropic cells in the dynamics of experimental immunostimulation. Proceedings of the CBU International Conference, Prague, Czech Republic.","DOI":"10.12955\/cbup.2013.47"},{"key":"ref_7","first-page":"75","article-title":"Ozone therapy in traumatology and burns treatment","volume":"3","author":"Peretyagin","year":"2013","journal-title":"Rev. Espa\u00f1ola Ozonoterapia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1208\/s12248-014-9687-3","article-title":"Strategic Approaches to Optimizing Peptide ADME Properties","volume":"17","author":"Di","year":"2015","journal-title":"AAPS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ebiom.2019.07.010","article-title":"Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse","volume":"46","author":"Sass","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1661e","DOI":"10.21769\/BioProtoc.1661","article-title":"da Skin Wound Healing Model - Excisional Wounding and Assessment of Lesion Area","volume":"5","author":"Moreira","year":"2015","journal-title":"Bio-Protocol."},{"key":"ref_11","first-page":"19","article-title":"Pharmacological correction of nonspecific resistance and production of proinflammatory cytokines during chronic intoxication with organophosphorus compound VX","volume":"75","author":"Grishin","year":"2012","journal-title":"Eksp. Klin. Farmakol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3103\/S1068367417010141","article-title":"Negative impact of Imunofan modulation on a result of specific therapy of helminthiases","volume":"43","author":"Mamykova","year":"2017","journal-title":"Russ. Agric. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"511","DOI":"10.31016\/978-5-9902340-8-6.2019.20.511-517","article-title":"Protective efficacy of a complex biopreparation based on a somatic extract of Trichinella and Imunofan in experimental trichnosis in white mice","volume":"20","author":"Rudneva","year":"2019","journal-title":"Theory Pract. Parasit. Dis. Control."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1046\/j.1524-475x.2000.00204.x","article-title":"Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508","volume":"8","author":"Stiernberg","year":"2000","journal-title":"Wound Repair Regen."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.orthres.2004.10.002","article-title":"Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis","volume":"23","author":"Wang","year":"2005","journal-title":"J. Orthop. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1046\/j.1523-1747.1999.00606.x","article-title":"Expression and activation of matrix metalloproteinases in wounds: Modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine- Cu2+","volume":"112","author":"Monier","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/648108","article-title":"GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration","volume":"2015","author":"Pickart","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1096\/fj.13-248476","article-title":"A potential wound-healing-promoting peptide from salamander skin","volume":"28","author":"Mu","year":"2014","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.biocel.2014.01.010","article-title":"A potential wound healing-promoting peptide from frog skin","volume":"49","author":"Liu","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tang, J., Liu, H., Gao, C., Mu, L., Yang, S., Rong, M., Zhang, Z., Liu, J., Ding, Q., and Lai, R. (2014). A small peptide with potential ability to promote wound healing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092082"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/2161334a0","article-title":"Binding of Cortisol to Human Albumin","volume":"216","author":"Pearson","year":"1967","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jchromb.2016.02.005","article-title":"Recognition and binding of \u03b2-lactam antibiotics to bovine serum albumin by frontal affinity chromatography in combination with spectroscopy and molecular docking","volume":"1014","author":"Li","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1172\/JCI105889","article-title":"Retinol-binding protein: The transport protein for vitamin A in human plasma","volume":"47","author":"Kanai","year":"1968","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2133\/dmpk.24.300","article-title":"Albumin as Fatty Acid Transporter","volume":"24","year":"2009","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0076-6879(86)28077-5","article-title":"Structure and lipid binding properties of serum albumin","volume":"128","author":"Spector","year":"1986","journal-title":"Meth. Enzymol."},{"key":"ref_26","unstructured":"Deptu\u0142a, M., Karpowicz, P., Wardowska, A., Sass, P., Sosnowski, P., Mieczkowska, A., Filipowicz, N., Dzier\u017cy\u0144ska, M., Sawicka, J., and Nowicka, E. (2019). Development of a Peptide Derived from Platelet-Derived Growth Factor (PDGF-BB) into a Potential Drug Candidate for the Treatment of Wounds. Adv. Wound Care, 1\u201319."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"368","DOI":"10.25122\/jml-2019-0068","article-title":"Immunological Methods for Treatment of Vulvovaginal Infections in the Preconception Period","volume":"12","author":"Alyautdina","year":"2019","journal-title":"J. Med. Life"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08923978709035198","article-title":"In Vitro Effects of Tp5 Analogs on E-Rosette Formation and Cell Division","volume":"9","author":"Denes","year":"1987","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1136\/adc.67.9.1095","article-title":"Thymopentin treatment in severe atopic dermatitis-clinical and immunological evaluations","volume":"67","author":"Hsieh","year":"1992","journal-title":"Arch. Dis. Child."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1002\/jps.21148","article-title":"Preparation and Evaluation of Poly-Butylcyanoacrylate Nanoparticles for Oral Delivery of Thymopentin","volume":"97","author":"He","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_31","first-page":"2","article-title":"Reciprocal control of cell proliferation and migration","volume":"8","author":"Ranaldi","year":"2010","journal-title":"Cell Commun. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nchembio.1383","article-title":"Designing immunogenic peptides","volume":"9","author":"Flower","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1006\/biol.2001.0308","article-title":"Antigenicity and immunogenicity of synthetic peptides","volume":"29","year":"2001","journal-title":"Biologicals"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hemshekhar, M., Anaparti, V., and Mookherjee, N. (2016). Functions of Cationic Host Defense Peptides in Immunity. Pharmaceuticals, 9.","DOI":"10.3390\/ph9030040"},{"key":"ref_35","first-page":"212","article-title":"Hypersensitivity reactions to biological drugs","volume":"24","author":"Corominas","year":"2014","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-1759(03)00206-0","article-title":"Strategies for detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals","volume":"278","author":"Wadhwa","year":"2003","journal-title":"J. Immunol. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibtech.2006.04.001","article-title":"Scientific and regulatory considerations on the immunogenicity of biologics","volume":"24","author":"Shankar","year":"2006","journal-title":"Trends Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/BF02446474","article-title":"Effect of the synthetic regulatory peptide thymohexin on the production of various classes of immunoglobulins","volume":"118","author":"Lebedev","year":"1994","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0134791","article-title":"DNA methylation dynamics regulate the formation of a regenerative wound epithelium during axolotl limb regeneration","volume":"10","author":"Aguilar","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/scrt39","article-title":"Role of Oct4 in maintaining and regaining stem cell pluripotency","volume":"1","author":"Shi","year":"2010","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature11925","article-title":"NANOG-dependent function of TET1 and TET2 in establishment of pluripotency","volume":"495","author":"Costa","year":"2013","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2144\/000112900","article-title":"Profiling the HeLa S3 transcriptome using randomly primed cDNA and massively parallel short-read sequencing","volume":"45","author":"Morin","year":"2008","journal-title":"Biotechniques"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/j.bmc.2017.01.004","article-title":"Cystatin C peptidomimetic derivative with antimicrobial properties as a potential compound against wound infections","volume":"25","author":"Krzystyniak","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_45","unstructured":"W\u00fcthrich, K. (1991). NMR of Proteins and Nucleic Acids, Wiley."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0006-291X(83)91225-1","article-title":"Improved spectral resoltion in cosy 1H NMR spectra proteins via double quantum filtering","volume":"117","author":"Rance","year":"1983","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","first-page":"177","article-title":"Enhanced NMR resolution by restricting the effective sample volume","volume":"37","author":"Bax","year":"1980","journal-title":"J. Magn. Reson."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-291X(80)90695-6","article-title":"A two-dimensional nuclear Overhauser enhancement (2D NOE) experiment for the elucidation proton-proton cross relaxation networks in biological macromolecules","volume":"95","author":"Kumar","year":"1980","journal-title":"Biochim. Biophys. Res. Commun."},{"key":"ref_49","first-page":"207","article-title":"Practical aspects of two-dimensional transverse NOE spectroscopy","volume":"63","author":"Bax","year":"1985","journal-title":"J. Magn. Reson."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF00197809","article-title":"NMRPipe: A multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"J. Biomol. NMR"},{"key":"ref_51","unstructured":"Goddard, T., and Kneller, D. (2001). SPARKY 3 2001, University of California. Available online: https:\/\/www.cgl.ucsf.edu\/home\/sparky\/."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10858-015-9921-z","article-title":"Combined automated NOE assignment and structure calculation with CYANA","volume":"62","author":"Buchner","year":"2015","journal-title":"J. Biomol. NMR"},{"key":"ref_53","unstructured":"Case, D., Darden, T., Simmerling, C., Cheatham, T.E., and Merz, K. (2011). Amber11 User\u2019s Manual, University of California."},{"key":"ref_54","unstructured":"DeLano, W.L. (2002). The PyMOL Molecular Graphics System, Schr\u00f6dinger, LLC. Version 1.5.0.4."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0179201","article-title":"Design of short peptides to block BTLA\/HVEM interactions for promoting anticancer T-cell responses","volume":"12","author":"Spodzieja","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-29477-5","article-title":"Immunophenotyping and transcriptional profiling of in vitro cultured human adipose tissue derived stem cells","volume":"8","author":"Mieczkowska","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1089\/ten.tec.2011.0216","article-title":"Adipogenesis of Human Adipose-Derived Stem Cells Within Three-Dimensional Hollow Fiber-Based Bioreactors","volume":"18","author":"Gerlach","year":"2012","journal-title":"Tissue Eng. Part. C Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jdermsci.2017.12.003","article-title":"Transcriptional profile of in vitro expanded human epidermal progenitor cells for the treatment of non-healing wounds","volume":"89","author":"Langa","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.peptides.2012.04.001","article-title":"Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin","volume":"35","author":"Karna","year":"2012","journal-title":"Peptides"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/(SICI)1098-2264(199708)19:4<201::AID-GCC1>3.0.CO;2-0","article-title":"Sustained nontumorigenic phenotype correlates with a largely stable chromosome content during long-term culture of the human keratinocyte line HaCat","volume":"19","author":"Boukamp","year":"1997","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.106.3.761","article-title":"Normal Keratinization in a Spontaneously Immortalized Aneuploid Human Keratinocyte Cell Line","volume":"106","author":"Boukamp","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"110426","DOI":"10.1016\/j.msec.2019.110426","article-title":"A vector-enzymatic DNA fragment amplification-expression technology for construction of artificial, concatemeric DNA, RNA and proteins for novel biomaterials, biomedical and industrial applications","volume":"108","author":"Skowron","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17995","DOI":"10.1038\/s41598-017-18203-2","article-title":"High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling","volume":"7","author":"Globus","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/stem.121","article-title":"Senescent Growth Arrest in Mesenchymal Stem Cells Is Bypassed by Wip1-Mediated Downregulation of Intrinsic Stress Signaling Pathways","volume":"27","author":"Lee","year":"2009","journal-title":"Stem Cells"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/cbdd.12688","article-title":"In Vitro Evaluation of the Allergic Potential of Antibacterial Peptides: Camel and Citropin","volume":"87","author":"Specjalski","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol."},{"key":"ref_67","unstructured":"Trapnell, C. (2018, August 14). Cufflinks. Available online: http:\/\/cole-trapnell-lab.github.io\/cufflinks\/manual\/."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_69","unstructured":"Rasband, W. (2018, August 14). ImageJ, Available online: https:\/\/imagej.nih.gov\/ij\/download.html."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/12\/2884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:41:33Z","timestamp":1760175693000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/12\/2884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,23]]},"references-count":69,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["molecules25122884"],"URL":"https:\/\/doi.org\/10.3390\/molecules25122884","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,23]]}}}