Hematopoietic progenitor and stem cells circulate by surfing on intracellular Ca 2+ waves: A novel target for cell-based therapy and anti-cancer treatment?

Francesco Moccia, Elisa Bonetti, Silvia Dragoni, Jacopo Fontana, Francesco Lodola, Roberto Berra Romani, Umberto Laforenza, Vittorio Rosti, Franco Tanzi

Research output: Contribution to journalArticle

Abstract

Hematopoietic progenitor and stem cells (HPSCs) have been employed in cell-based therapy (CBT) to promote neovascularisation and regeneration of ischemic organs, such as heart and limbs. Furthermore, endothelial progenitor cells (EPCs) may favour tumour growth and adverse vascular targeting treatment by incorporating into neovessels. CBT is hampered by the paucity of HPSCs harvested from peripheral blood and suffers from several pitfalls, including the differentiation outcome of transplanted cells and low percentage of engrafted cells. Therefore, CBT will benefit of a better understanding of the signal transduction pathway(s) which drive(s) HPSC homing, proliferation and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to combat tumoral neovascularisation. The elevation in intracellular Ca 2+ concentration is the key signal in the regulation of cellular motility, replication, and differentiation. Intracellular Ca 2+ waves regulate cytoskeleton re-organisation and disassembly at focal adhesions, thus stimulating migration and substrate adhesion, and induce DNA transcription by recruiting Ca 2+-sensitive transcription factors. However, the Ca 2+ signalling toolkit which underlies Ca 2+ release from intracellular stores and Ca 2+ entry across the plasmalemma in HPSCs is still unclear. Our recent work has shown that the so-called store-operated Ca 2+ entry stimulates EPC growth. Unravelling the mechanisms guiding HPSC behaviour might supply the biological bases required to improve CBT. For instance, genetic manipulation of the Ca 2+ signalling machinery (such as transfer of genes encoding for the Ca 2+ channels involved in EPC proliferation) could provide a novel approach to increase the extent of limb neovascularisation and regeneration of damaged hearts.

Original languageEnglish
Pages (from-to)161-176
Number of pages16
JournalCurrent Signal Transduction Therapy
Volume7
Issue number2
Publication statusPublished - May 2012

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Keywords

  • Ca signalling
  • Cell-based therapy
  • Cyclic ADP-ribose
  • Endothelial progenitor cells
  • Gene-based therapy
  • Pematopoietic stem cells
  • Snositol-1,4,5-trisphosphate
  • Store-operated Ca entry
  • Stromal derived factor-1
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Endocrinology
  • Pharmacology (medical)

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