title: Macrophages regulate smooth muscle differentiation of mesenchymal stem cells via a prostaglandin F₂α-mediated paracrine mechanism.
abstract: OBJECTIVE
  Mesenchymal stem cells are useful for vascular regeneration of injured tissues. Macrophages are involved in acute or chronic inflammatory diseases, and interleukin-1β (IL-1β), a proinflammatory cytokine, plays a key role in the activation of macrophages within injured tissues. To explore the role of macrophages on mesenchymal stem cell-mediated vascular regeneration, we examined the effects of IL-1β-activated macrophages on differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to smooth muscle cells (SMCs) and the vascular regenerative capacity of the differentiated SMCs in a hindlimb ischemia animal model.
  
  
  RESULTS
  We demonstrate that IL-1β-conditioned medium from RAW 264.7 macrophages induces differentiation of human adipose tissue-derived mesenchymal stem cells to α-smooth muscle actin-positive SMCs, and the differentiated SMCs exhibited increased contractility in response to KCl and carbachol treatment. Transplantation of the differentiated SMCs attenuated severe hindlimb ischemia and promoted vascular regeneration. IL-1β treatment stimulated secretion of prostaglandin F(2α) from RAW 264.7 cells. Small interfering RNA-mediated silencing of the prostaglandin F(2α) receptor completely abrogated IL-1β conditioned medium-stimulated α-smooth muscle actin expression. Moreover, prostaglandin F(2α) treatment stimulated expression of α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells.
  
  
  CONCLUSIONS
  These results suggest that IL-1β-activated macrophages promote differentiation of human adipose tissue-derived mesenchymal stem cells to SMCs through a prostaglandin F(2α)-mediated paracrine mechanism.
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Yang Woo
authors.initials: YW
authors.lastname: Kwon
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Do
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Park
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lee
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism*; D004195:Disease Models, Animal; D006614:Hindlimb; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007511:Ischemia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D034622:RNA Interference; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D014162:Transfection
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost