Cellular direct conversion by cell penetrable OCT4-30Kc19 protein and BMP4 growth factor

• DOI: 10.1186/s40824-022-00280-8
• Publication Date: 2022-07-14T11:03:04Z
• Authors: Seung Hyun L. Kim; Sungwoo Cho; Seoyeon Kim; Janet Kwon; Jaeyoung Lee; Rachel H. Koh; Ju Hyun Park; Hwajin Lee; Tai Hyun Park; Nathaniel S. Hwang
• Keywords: Transdifferentiation

The number of patients suffering from osteoporosis is increasing as the elderly population increases. demand for investigating bone regeneration strategies naturally arises. One approaches to induce somatic cell transdifferentiation. Among transcriptional regulators transdifferentiation, octamer-binding transcription factor 4 (OCT4) famous its role in regulation pluripotency stem cells. Bone morphogenetic protein (BMP4) another that known have a significant osteogenic differentiation. Previous studies achieved transdifferentiation cells into osteoblasts using viral and plasmid deliveries these factors. Although methods are efficient, transfection safety issues such permanent gene incorporations bacterial DNA insertions. Herein, we developed penetrating protein-based strategy endothelial via nuclear delivery OCT4 recombinant combined with BMP4 treatment. For protein, fused 30Kc19, cell-penetrating stabilizing derived silkworm hemolymph Bombyx mori low cytotoxic properties. This study proposes promising cell-based therapy without any existing had.OCT4-30Kc19 high activities stability was synthesized system. Cells were treated OCT4-30Kc19 evaluate their cellular activity, cytotoxicity, angiogenic potentials vitro. potential 3D spheroids also analyzed. In addition, vivo subcutaneous tissue cranial defect model performed.OCT4-30Kc19 produced soluble stable form. efficiently penetrated localized intracellular compartments nucleus. delivered showed increased osteogenesis, both 2D culture, angiogenesis capacity Results cell-seeded scaffolds confirmed enhanced properties transdifferentiated HUVECs treatment BMP4. mouse experiment demonstrated successful pretreated BMP4.Using method allows an alternative approach utilizing genetic modification strategies, thus providing possibility safer use therapies clinical applications.