Exploiting human CD34+ stem cell-conditioned medium for tissue repair

Paul J. Mintz, Kai Wen Huang, Vikash Reebye, Georgios Nteliopoulos, Hong Shiee Lai, Pal Sætrom, Noriyuki Kasahara, Steen Jensen, Madhava Pai, Myrtle Y.A. Gordon, Stephen B. Marley, Rosemary Behan, Duncan R. Spalding, Abdelali Haoudi, Mohamed M. Emara, Joanna Nicholls, John J. Rossi, Nagy A. Habib

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34 + cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34 + cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34 + cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-kit, and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signaling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34 + cells has the potential for therapeutic repair of damaged tissue in vivo.

Original languageEnglish (US)
Pages (from-to)149-159
Number of pages11
JournalMolecular Therapy
Volume22
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Mintz, P. J., Huang, K. W., Reebye, V., Nteliopoulos, G., Lai, H. S., Sætrom, P., Kasahara, N., Jensen, S., Pai, M., Gordon, M. Y. A., Marley, S. B., Behan, R., Spalding, D. R., Haoudi, A., Emara, M. M., Nicholls, J., Rossi, J. J., & Habib, N. A. (2014). Exploiting human CD34+ stem cell-conditioned medium for tissue repair. Molecular Therapy, 22(1), 149-159. https://doi.org/10.1038/mt.2013.194