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Direct Reprogramming of Mouse Fibroblasts into Melanocytes
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Direct cell reprogramming for tissue engineering and regenerative medicine.

Alexander Grath1, Guohao Dai1

  • 1Department of Bioengineering, Northeastern University, Lake Hall 214A, 360 Huntington Avenue, Boston, MA 02115 USA.

Journal of Biological Engineering
|February 27, 2019
PubMed
Summary
This summary is machine-generated.

Direct cell reprogramming (transdifferentiation) offers a promising path for tissue engineering by converting abundant cells into needed types. This avoids pluripotency and shows potential for treating injuries and diseases, with CRISPR/Cas9 enhancing efficiency.

Keywords:
Cell reprogrammingEpigeneticsGene editingStem cellsTissue engineeringTransdifferentiation

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Area of Science:

  • Cellular reprogramming and regenerative medicine
  • Biotechnology and tissue engineering
  • Somatic cell conversion strategies

Background:

  • Terminally differentiated cells often lose proliferation capacity, hindering tissue repair in conditions like heart attacks and neurodegenerative diseases.
  • Direct cell reprogramming (transdifferentiation) bypasses induced pluripotency, converting one somatic cell type directly into another.
  • This approach is vital for regenerative medicine when endogenous cell proliferation is insufficient for healing.

Purpose of the Study:

  • To review recent advancements in direct cell reprogramming techniques.
  • To explore the application of transdifferentiation in generating various cell phenotypes for tissue repair.
  • To discuss the challenges and potential solutions for clinical translation of transdifferentiation therapies.

Main Methods:

  • Overexpression of transcription factors using viral vectors (e.g., lentivirus).
  • Small molecules for inducing cellular fate changes.
  • CRISPR/Cas9 technology, including fusion with transcriptional modulators, for genetic and epigenetic reprogramming.
  • In vivo and in situ generation of transdifferentiated cells.

Main Results:

  • Transdifferentiation has successfully generated diverse cell types, including endothelial, neuronal, and skeletal muscle cells.
  • These reprogrammed cells can functionally mimic mature adult cells and promote tissue regeneration in vivo.
  • Successful preclinical applications observed in mouse models for liver and brain diseases, and in engineered vascular grafts.

Conclusions:

  • Direct cell reprogramming is a powerful tool in regenerative medicine and tissue engineering.
  • CRISPR/Cas9-based methods show enhanced reprogramming efficiency compared to traditional viral vectors.
  • While clinical applications are pending, ongoing research and in situ generation strategies offer significant promise for future therapies.