{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T01:09:01Z","timestamp":1778202541053,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T00:00:00Z","timestamp":1446768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing\/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.<\/jats:p>","DOI":"10.3390\/ijms161125986","type":"journal-article","created":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T11:12:15Z","timestamp":1446808335000},"page":"26667-26676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Taku","family":"Kaitsuka","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Kumamoto 860-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhito","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Kumamoto 860-8556, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.copbio.2011.03.008","article-title":"Protein transduction domain delivery of therapeutic macromolecules","volume":"22","author":"Dowdy","year":"2011","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nrg2071","article-title":"The origin of eukaryotes: A reappraisal","volume":"8","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.ymthe.2004.08.010","article-title":"Cellular uptake of arginine-rich peptides: Roles for macropinocytosis and actin rearrangement","volume":"10","author":"Nakase","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2004.10.018","article-title":"Cationic TAT peptide transduction domain enters cells by macropinocytosis","volume":"102","author":"Kaplan","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrm2447","article-title":"Shaping cups into phagosomes and macropinosomes","volume":"9","author":"Swanson","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/0092-8674(88)90263-2","article-title":"Cellular uptake of the tat protein from human immunodeficiency virus","volume":"55","author":"Frankel","year":"1988","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/0092-8674(88)90262-0","article-title":"Autonomous functional domains of chemically synthesized human immunodeficiency virus TAT trans-activator protein","volume":"55","author":"Green","year":"1988","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1073\/pnas.88.5.1864","article-title":"Antennapedia homeobox peptide regulates neural morphogenesis","volume":"88","author":"Joliot","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1021\/bc015508l","article-title":"Stearylated arginine-rich peptides: A new class of transfection systems","volume":"12","author":"Futaki","year":"2001","journal-title":"Bioconjug. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6000","DOI":"10.1523\/JNEUROSCI.21-16-06000.2001","article-title":"A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation","volume":"21","author":"Matsushita","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1016\/j.biomaterials.2012.02.049","article-title":"A protein transduction method using oligo-arginine (3R) for the delivery of transcription factors into cell nuclei","volume":"33","author":"Hitsuda","year":"2012","journal-title":"Biomaterials"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1074\/jbc.M006701200","article-title":"Internalization of HIV-1 TAT requires cell surface heparan sulfate proteoglycans","volume":"276","author":"Tyagi","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1074\/jbc.M110017200","article-title":"Possible existence of common internalization mechanisms among arginine-rich peptides","volume":"277","author":"Suzuki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nm996","article-title":"Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis","volume":"10","author":"Wadia","year":"2004","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10581","DOI":"10.1074\/jbc.M110.187450","article-title":"Single particle tracking confirms that multivalent Tat protein transduction domain-induced heparan sulfate proteoglycan cross-linkage activates Rac1 for internalization","volume":"286","author":"Imamura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1074\/jbc.M109.021964","article-title":"Revised role of glycosaminoglycans in TAT protein transduction domain-mediated cellular transduction","volume":"285","author":"Gump","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/mt.2011.313","article-title":"Transient focal membrane deformation induced by arginine-rich peptides leads to their direct penetration into cells","volume":"20","author":"Hirose","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/j.bbamem.2013.05.016","article-title":"Effects of pyrenebutyrate on the translocation of arginine-rich cell-penetrating peptides through artificial membranes: Recruiting peptides to the membranes, dissipating liquid-ordered phases, and inducing curvature","volume":"1828","author":"Katayama","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1146\/annurev.biochem.78.081307.110540","article-title":"Mechanisms of endocytosis","volume":"78","author":"Doherty","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e86639","DOI":"10.1371\/journal.pone.0086639","article-title":"COPA and SLC4A4 are required for cellular entry of arginine-rich peptides","volume":"9","author":"Tsumuraya","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.cell.2015.03.028","article-title":"Efficient intracellular delivery of native proteins","volume":"161","author":"Pagliero","year":"2015","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nbt.3081","article-title":"Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo","volume":"33","author":"Zuris","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrg2141","article-title":"Engineering targeted viral vectors for gene therapy","volume":"8","author":"Waehler","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nature07864","article-title":"Virus-free induction of pluripotency and subsequent excision of reprogramming factors","volume":"458","author":"Kaji","year":"2009","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nature07863","article-title":"piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells","volume":"458","author":"Woltjen","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cell.2005.07.013","article-title":"Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice","volume":"122","author":"Ding","year":"2005","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14981","DOI":"10.1073\/pnas.0607282103","article-title":"The piggyBac transposon holds promise for human gene therapy","volume":"103","author":"Feschotte","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"420","DOI":"10.5966\/sctm.2012-0139","article-title":"Lineage-specific purification of neural stem\/progenitor cells from differentiated mouse induced pluripotent stem cells","volume":"2","author":"Maruyama","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_30","unstructured":"Kaitsuka, T., and Tomizawa, K. (2015). Generation of functional insulin-producing cells from human pluripotent stem cells via protein transduction methods, Manuscript in preparation."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1242\/dev.103952","article-title":"Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition","volume":"141","author":"Sun","year":"2014","journal-title":"Development"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrm2009","article-title":"Notch signalling: A simple pathway becomes complex","volume":"7","author":"Bray","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrm3244","article-title":"Endocytic control of growth factor signalling: Multivesicular bodies as signalling organelles","volume":"13","author":"Dobrowolski","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrm3470","article-title":"The complex world of WNT receptor signalling","volume":"13","author":"Niehrs","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1634\/stemcells.2007-0482","article-title":"Connexin expression and functional analysis of gap junctional communication in mouse embryonic stem cells","volume":"26","author":"Maxeiner","year":"2008","journal-title":"Stem Cells"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21512","DOI":"10.1074\/jbc.273.34.21512","article-title":"Structural requirements for PAK activation by Rac GTPases","volume":"273","author":"Knaus","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C1159","DOI":"10.1152\/ajpcell.00496.2009","article-title":"Laminin regulates mouse embryonic stem cell migration: Involvement of Epac1\/Rap1 and Rac1\/cdc42","volume":"298","author":"Suh","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1126\/science.3090687","article-title":"Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins","volume":"233","author":"Feramisco","year":"1986","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nature12138","article-title":"Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells","volume":"497","author":"Commisso","year":"2013","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nature01646","article-title":"Role of ERas in promoting tumour-like properties in mouse embryonic stem cells","volume":"423","author":"Takahashi","year":"2003","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.stem.2013.04.009","article-title":"Next-generation regenerative medicine: Organogenesis from stem cells in 3D culture","volume":"12","author":"Sasai","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.stemcr.2013.12.007","article-title":"Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application","volume":"2","author":"Kamao","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.stemcr.2014.07.005","article-title":"Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells","volume":"3","author":"Gotoh","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cell.2014.09.040","article-title":"Generation of functional human pancreatic beta cells in vitro","volume":"159","author":"Pagliuca","year":"2014","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.5966\/sctm.2013-0075","article-title":"Generation of functional insulin-producing cells from mouse embryonic stem cells through 804G cell-derived extracellular matrix and protein transduction of transcription factors","volume":"3","author":"Kaitsuka","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.2337\/diabetes.52.7.1732","article-title":"PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells","volume":"52","author":"Noguchi","year":"2003","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.2337\/diabetes.54.10.2859","article-title":"BETA2\/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence","volume":"54","author":"Noguchi","year":"2005","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/jmcb\/mju029","article-title":"Generation of insulin-producing beta-like cells from human iPS cells in a defined and completely xeno-free culture system","volume":"6","author":"Shahjalal","year":"2014","journal-title":"J. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/nbt.3033","article-title":"Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells","volume":"32","author":"Rezania","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","article-title":"Rapid single-step induction of functional neurons from human pluripotent stem cells","volume":"78","author":"Zhang","year":"2013","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nature11525","article-title":"Generation of functional thyroid from embryonic stem cells","volume":"491","author":"Antonica","year":"2012","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2013.03.004","article-title":"Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner","volume":"12","author":"Chan","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e61540","DOI":"10.1371\/journal.pone.0061540","article-title":"Efficient and reproducible myogenic differentiation from human iPS cells: Prospects for modeling Miyoshi Myopathy in vitro","volume":"8","author":"Tanaka","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3727\/096368912X653057","article-title":"The combined expression of Pdx1 and MafA with either Ngn3 or NeuroD improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells","volume":"22","author":"Xu","year":"2013","journal-title":"Cell Transplant."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1007\/s00018-010-0347-1","article-title":"Transcription factor-based modulation of neural stem cell differentiation using direct protein transduction","volume":"67","author":"Stock","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.bbrc.2012.09.090","article-title":"Induction of motor neuron differentiation by transduction of Olig2 protein","volume":"427","author":"Mie","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.brainres.2008.02.065","article-title":"TAT-PAX6 protein transduction in neural progenitor cells: A novel approach for generation of dopaminergic neurones in vitro","volume":"1208","author":"Spitere","year":"2008","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jbiosc.2011.08.025","article-title":"Effects of protein transduction with intact myogenic transcription factors tagged with HIV-1 Tat-PTD (T-PTD) on myogenic differentiation of mouse primary cells","volume":"113","author":"Hidema","year":"2012","journal-title":"J. Biosci. Bioeng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbrc.2009.03.060","article-title":"Transduction of MyoD protein into myoblasts induces myogenic differentiation without addition of protein transduction domain","volume":"382","author":"Noda","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1073\/pnas.032068699","article-title":"Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: A tool for efficient genetic engineering of mammalian genomes","volume":"99","author":"Peitz","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nmeth884","article-title":"Site-specific recombination in human embryonic stem cells induced by cell-permeant Cre recombinase","volume":"3","author":"Nolden","year":"2006","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/stem.417","article-title":"Engineering cell-permeant FLP recombinase for tightly controlled inducible and reversible overexpression in embryonic stem cells","volume":"28","author":"Patsch","year":"2010","journal-title":"Stem Cells"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1101\/gr.171264.113","article-title":"Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA","volume":"24","author":"Ramakrishna","year":"2014","journal-title":"Genome Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nbt.1541","article-title":"Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein","volume":"27","author":"Eguchi","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature05944","article-title":"In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state","volume":"448","author":"Wernig","year":"2007","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/scrt435","article-title":"Excision of viral reprogramming cassettes by Cre protein transduction enables rapid, robust and efficient derivation of transgene-free human induced pluripotent stem cells","volume":"5","author":"Kadari","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/embor.2011.88","article-title":"E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming","volume":"12","author":"Redmer","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Qin, Y., and Gao, W.Q. (2015). Concise Reviews: Patient-Derived Stem Cell Research for Monogenic Disorders. Stem Cells.","DOI":"10.1002\/stem.2112"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/dgd.12107","article-title":"Genetic correction using engineered nucleases for gene therapy applications","volume":"56","author":"Li","year":"2014","journal-title":"Dev. Growth Differ."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.stem.2009.04.005","article-title":"Generation of induced pluripotent stem cells using recombinant proteins","volume":"4","author":"Zhou","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.stem.2009.05.005","article-title":"Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins","volume":"4","author":"Kim","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1182\/blood-2010-02-269589","article-title":"Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation","volume":"116","author":"Cho","year":"2010","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1038\/srep04361","article-title":"Partial somatic to stem cell transformations induced by cell-permeable reprogramming factors","volume":"4","author":"Lim","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/nature08797","article-title":"Direct conversion of fibroblasts to functional neurons by defined factors","volume":"463","author":"Vierbuchen","year":"2010","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2010.07.002","article-title":"Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors","volume":"142","author":"Ieda","year":"2010","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature10116","article-title":"Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors","volume":"475","author":"Huang","year":"2011","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/nature10263","article-title":"Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors","volume":"475","author":"Sekiya","year":"2011","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nbt.2564","article-title":"Generation of oligodendroglial cells by direct lineage conversion","volume":"31","author":"Yang","year":"2013","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/11\/25986\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:51:36Z","timestamp":1760215896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/16\/11\/25986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,6]]},"references-count":78,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11]]}},"alternative-id":["ijms161125986"],"URL":"https:\/\/doi.org\/10.3390\/ijms161125986","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,6]]}}}