The influence of extracellular matrix proteins and mesenchymal stem cells on erythropoietic cell maturation

Vox Sang. 2011 Jul;101(1):65-76. doi: 10.1111/j.1423-0410.2010.01453.x. Epub 2010 Dec 22.

Abstract

Background and objectives: As part of the bone marrow niche, cellular and acellular components like mesenchymal stem cells (MSCs) and extracellular matrix (ECM) proteins influence human haematopoiesis. To identify factors able to improve the in vitro generation of red blood cells (RBCs), we investigated the effect of these factors on proliferation and differentiation of human haematopoietic stem cells (HSCs) into erythroid cells.

Material and methods: Granulocyte colony-stimulating factor-mobilized CD34(+) HSCs were cultured for 16 days using an in vitro erythropoiesis assay as described previously (by our group). The HSCs were co-cultured with MSCs in either direct or indirect contact and with different ECM proteins (fibronectin, laminin, collagen and a mixture of ECM proteins, called ECM gel).

Results: Co-culturing of HSCs with ECM gel improved cell viability, and the presence of laminin slightly increased the maturation into enucleated RBCs. HSC expansion could not be improved by addition of any of the ECM proteins investigated. In contrast, fibronectin inhibited erythroid formation. Co-culturing of HSCs with MSCs generally stimulated cell viability and HSC proliferation, however, in favour of the myeloid lineage. In summary, of all investigated factors, only laminin and ECM gel had a supportive effect on RBC development under the described in vitro culture conditions.

MeSH terms

  • Antigens, CD34 / metabolism
  • Antigens, CD34 / pharmacology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Fibronectins / metabolism
  • Fibronectins / pharmacology
  • Glycophorins / metabolism
  • Glycophorins / pharmacology
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Interleukin-16 / metabolism
  • Laminin / metabolism*
  • Laminin / pharmacology
  • Mesenchymal Stem Cells / metabolism*

Substances

  • Antigens, CD34
  • Extracellular Matrix Proteins
  • Fibronectins
  • Glycophorins
  • Interleukin-16
  • Laminin
  • Granulocyte Colony-Stimulating Factor