title: Hepatocyte growth factor mobilizes non-bone marrow-derived circulating mesoangioblasts.
abstract: OBJECTIVE
  The identification of factors that mobilize subsets of endogenous progenitor cells may provide new therapeutic tools to enhance the repair of ischaemic tissue. We previously identified circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs) in children undergoing heart surgery with cardiopulmonary bypass (CPB). However, the mechanisms by which these cells are mobilized and their origin is unclear.
  
  
  RESULTS
  Circulating CD73(+)CD45(-)KDR(+) cMABs were analysed in adults undergoing heart surgery with (n = 21) or without CPB (n = 8). During surgery with CPB, cMABs are mobilized with a maximal response at the end of the operation. In contrast, off-pump heart surgery does not stimulate cMAB mobilization, indicating that the stress mediated by CPB induces the mobilization of cMAB. Circulating mesoangioblasts were enriched in blood obtained from the coronary sinus. Histologically, CD73(+) cells were detected around vessels in the heart, indicating that the heart is one of the niches of cMABs. Consistently, studies in gender mismatched bone marrow transplanted patients demonstrated that cMABs did not originate from the bone marrow. Cytokine profiling of serum samples revealed that hepatocyte growth factor (HGF) was profoundly increased at the time point of maximal mobilization of cMABs. Hepatocyte growth factor stimulated the migration of cMABs. Importantly, injection of recombinant HGF increased cMABs in rats.
  
  
  CONCLUSIONS
  Hepatocyte growth factor induces mobilization of non-haematopoietic progenitor cells with a cardiac repair capacity. This newly identified function together with the known pleiotrophic effects of HGF makes HGF an attractive therapeutic option for the treatment of ischaemic heart disease.
authors.affiliation: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University, Frankfurt, Germany.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Hans
authors.initials: H
authors.lastname: Kossmann
authors.forename: Nadejda
authors.initials: N
authors.lastname: Monsefi
authors.forename: Stefan
authors.initials: S
authors.lastname: Rupp
authors.forename: Janina
authors.initials: J
authors.lastname: Trauth
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
authors.forename: Rebekka
authors.initials: R
authors.lastname: Goetz
authors.forename: Stefan
authors.initials: S
authors.lastname: Momma
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Kisho
authors.initials: K
authors.lastname: Ohtani
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schranz
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Sven
authors.initials: S
authors.lastname: Martens
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000368:Aged; D000818:Animals; D002315:Cardiopulmonary Bypass; D002454:Cell Differentiation / Q000187:drug effects*; D002648:Child; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008026:Ligation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor