Efficient in vitro generation of adult multipotent cells from mobilized peripheral blood CD133+ cells

Cell Prolif. 2008 Feb;41(1):12-27. doi: 10.1111/j.1365-2184.2007.00502.x.

Abstract

Objectives: To generate non-haematopoietic tissues from mobilized haematopoietic CD133(+) stem cells.

Materials and methods: Mobilized peripheral blood CD133(+) cells from adult healthy donors were used. In vitro ability of highly enriched CD133(+) cells from mobilized peripheral blood to generate multipotent cells, and their potential to give rise to cells with characteristics of neuroectoderm, endoderm and mesoderm layers was investigated.

Results: We found that a recently identified population of CD45(+) adherent cells generated in vitro after culture of highly purified CD133(+) cells for 3-5 weeks with Flt3/Flk2 ligand and interleukin-6 can, in presence of the appropriate microenvironmental cues, differentiate into neural progenitor-like cells (NPLCs), hepatocyte-like cells and skeletal muscle-like cells. We have termed them to be adult multipotent haematopoietic cells (AMHCs). AMHC-derived NPLCs expressed morphological, phenotypic and molecular markers associated with primary neural progenitor cells. They can differentiate into astrocyte-like cells, neuronal-like cells and oligodendrocyte-like cells. Moreover, AMHC-derived NPLCs produced 3,4-dihydrophenylalanine and dopamine and expressed voltage-activated ion channels, suggesting their functional maturation. In addition, AMHC-derived hepatocyte-like cells and skeletal muscle-like cells, showed typical morphological features and expressed primary tissue-associated proteins.

Conclusion: Our data demonstrate that AMHCs may therefore serve as a novel source of adult multipotent cells for autologous replacement cell therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Antigens, CD / immunology*
  • Base Sequence
  • Cell Differentiation
  • Chromatography, High Pressure Liquid
  • DNA Primers
  • Dihydroxyphenylalanine / biosynthesis
  • Dopamine / biosynthesis
  • Glycoproteins / immunology*
  • Humans
  • In Vitro Techniques
  • Multipotent Stem Cells / cytology*
  • Multipotent Stem Cells / immunology
  • Patch-Clamp Techniques
  • Peptides / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • AC133 Antigen
  • Antigens, CD
  • DNA Primers
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Dihydroxyphenylalanine
  • Dopamine