Nongenetic method for purifying stem cell-derived cardiomyocytes

Nat Methods. 2010 Jan;7(1):61-6. doi: 10.1038/nmeth.1403. Epub 2009 Nov 29.

Abstract

Several applications of pluripotent stem cell (PSC)-derived cardiomyocytes require elimination of undifferentiated cells. A major limitation for cardiomyocyte purification is the lack of easy and specific cell marking techniques. We found that a fluorescent dye that labels mitochondria, tetramethylrhodamine methyl ester perchlorate, could be used to selectively mark embryonic and neonatal rat cardiomyocytes, as well as mouse, marmoset and human PSC-derived cardiomyocytes, and that the cells could subsequently be enriched (>99% purity) by fluorescence-activated cell sorting. Purified cardiomyocytes transplanted into testes did not induce teratoma formation. Moreover, aggregate formation of PSC-derived cardiomyocytes through homophilic cell-cell adhesion improved their survival in the immunodeficient mouse heart. Our approaches will aid in the future success of using PSC-derived cardiomyocytes for basic and clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Callithrix
  • Cell Differentiation
  • Cell Separation / methods*
  • Cell Transplantation
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Flow Cytometry
  • Fluorescent Dyes / analysis
  • Heart / embryology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitochondria / metabolism
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / transplantation
  • Rats
  • Rhodamines / analysis
  • Staining and Labeling / methods*

Substances

  • Fluorescent Dyes
  • Rhodamines
  • tetramethylrhodamine methyl ester