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

Seung Hyun L Kim1,2, Sungwoo Cho3, Seoyeon Kim3

  • 1Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.

Biomaterials Research
|July 14, 2022
PubMed
Summary

This study developed a safe, protein-based method for cell transdifferentiation into bone-forming cells. The approach uses OCT4-30Kc19 protein and BMP4 to promote bone regeneration without genetic modification.

Keywords:
AngiogenesisCell penetrating proteinHUVECsOsteogenesisTransdifferentiation

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Area of Science:

  • Biotechnology
  • Regenerative Medicine
  • Cell Biology

Background:

  • Osteoporosis is a growing concern with an aging population, necessitating bone regeneration strategies.
  • Somatic cell transdifferentiation is a promising approach, with OCT4 and BMP4 known regulators.
  • Existing viral and plasmid methods for transdifferentiation pose safety risks like permanent gene incorporation.

Purpose of the Study:

  • To develop a safe, non-genetic cell-penetrating protein-based strategy for inducing osteogenic transdifferentiation.
  • To investigate the efficacy of nuclear delivery of OCT4 recombinant protein combined with BMP4 treatment.
  • To overcome the safety limitations of current gene delivery methods for cell-based therapies.

Main Methods:

  • Synthesized a stable, cell-penetrating OCT4-30Kc19 protein for osteogenic transdifferentiation.
  • Evaluated cellular uptake, cytotoxicity, osteogenic, and angiogenic potentials of OCT4-30Kc19 and BMP4 in vitro.
  • Assessed osteogenic potential in 3D spheroids and performed in vivo delivery in subcutaneous and cranial defect models.

Main Results:

  • OCT4-30Kc19 protein was successfully synthesized, demonstrating high stability and cellular/nuclear penetration.
  • Combined treatment with OCT4-30Kc19 and BMP4 significantly enhanced osteogenesis and angiogenesis in vitro.
  • In vivo studies confirmed enhanced bone regeneration in subcutaneous and cranial defect models using transdifferentiated cells.

Conclusions:

  • A protein-based transdifferentiation method offers a safe alternative to genetic modification for cell-based therapies.
  • This strategy holds promise for clinical applications in bone regeneration without safety concerns of viral or plasmid delivery.