Induced Pluripotent Stem Cells: Hope in the Treatment of Diseases, including Muscular Dystrophies

Int J Mol Sci. 2020 Jul 30;21(15):5467. doi: 10.3390/ijms21155467.

Abstract

Induced pluripotent stem (iPS) cells are laboratory-produced cells that combine the biological advantages of somatic adult and stem cells for cell-based therapy. The reprogramming of cells, such as fibroblasts, to an embryonic stem cell-like state is done by the ectopic expression of transcription factors responsible for generating embryonic stem cell properties. These primary factors are octamer-binding transcription factor 4 (Oct3/4), sex-determining region Y-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and the proto-oncogene protein homolog of avian myelocytomatosis (c-Myc). The somatic cells can be easily obtained from the patient who will be subjected to cellular therapy and be reprogrammed to acquire the necessary high plasticity of embryonic stem cells. These cells have no ethical limitations involved, as in the case of embryonic stem cells, and display minimal immunological rejection risks after transplant. Currently, several clinical trials are in progress, most of them in phase I or II. Still, some inherent risks, such as chromosomal instability, insertional tumors, and teratoma formation, must be overcome to reach full clinical translation. However, with the clinical trials and extensive basic research studying the biology of these cells, a promising future for human cell-based therapies using iPS cells seems to be increasingly clear and close.

Keywords: cellular therapy; induced pluripotent stem cells; muscular dystrophy; regeneration; stem cells.

Publication types

  • Review

MeSH terms

  • Cellular Reprogramming / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / transplantation*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / pathology
  • Muscular Dystrophies / therapy*
  • Organic Cation Transport Proteins / genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics
  • SOXB1 Transcription Factors / genetics

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MAS1 protein, human
  • MYC protein, human
  • Organic Cation Transport Proteins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • solute carrier family 22 (organic cation transporter), member 3