title: Characterization of menstrual stem cells: angiogenic effect, migration and hematopoietic stem cell support in comparison with bone marrow mesenchymal stem cells.
abstract: BACKGROUND
  Stem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity. Besides, menstrual fluid has important advantages over other sources for the isolation of MSCs, including ease of access and repeated sampling in a noninvasive manner. Such attributes allow the rapid culture of MenSCs in numbers that are sufficient for therapeutical doses, at lower cell passages.
  
  
  METHODS
  In this study, we advance the characterization of MenSC populations in comparison to bone marrow derived mesenchymal stem cells (BM-MSCs) with regards to proliferation, lineage differentiation, migration potential, secretion profile and angiogenic properties in vitro and in a matrigel plug assay in mice. We additionally tested their ability to support hematopoietic stem cell (HSC) expansion in vitro.
  
  
  RESULTS
  The phenotypic analysis of MenSCs revealed a profile largely similar to the BM-MSCs with the exception of a higher expression of the adhesion molecule CD49a (alpha1-integrin). Furthermore, the fibroblast colony forming units (CFU-F) from MenSCs yielded a 2 to 4 fold higher frequency of progenitors and their in vitro migration capacity was superior to BM-MSCs. In addition, MenSCs evidenced a superior paracrine response to hypoxic conditions as evidenced by the secretion of vascular endothelial growth factor and basic fibroblast growth factor and also improved angiogenic effect of conditioned media on endothelial cells. Furthermore, MenSCs were able to induce angiogenesis in a matrigel plug assay in vivo. Thus, an 8-fold increase in hemoglobin content was observed in implanted plugs containing MenSCs compared to BM-MSCs. Finally, we demonstrated, for the first time, the capacity of MenSCs to support the ex-vivo expansion of HSCs, since higher expansion rates of the CD34+CD133+ population as well as higher numbers of early progenitor (CFU-GEMM) colonies were observed in comparison to the BM source.
  
  
  CONCLUSIONS
  We present evidence showing superiority of MenSCs with respect to several functional aspects, in comparison with BM-MSCs. However, the impact of such properties in their use as adult-derived stem cells for regenerative3 medicine remains to be clarified.
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile. falcayaga@uandes.cl.|Cells for Cells, Santiago, Chile. falcayaga@uandes.cl.
authors.forename: Francisca
authors.initials: F
authors.lastname: Alcayaga-Miranda
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile. jcuenca@uandes.cl.|Cells for Cells, Santiago, Chile. jcuenca@uandes.cl.
authors.forename: Jimena
authors.initials: J
authors.lastname: Cuenca
authors.affiliation: Cells for Cells, Santiago, Chile. patricia.luz-crawford@inserm.fr.|Inserm, U844, Montpellier, F-34295, France. patricia.luz-crawford@inserm.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Luz-Crawford
authors.affiliation: Cells for Cells, Santiago, Chile. carolina.aguila.d@gmail.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aguila-Díaz
authors.affiliation: Cells for Cells, Santiago, Chile. ainoa.fo@c4c.cl.
authors.forename: Ainoa
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile. ffigueroa@uandes.cl.
authors.forename: Fernando E
authors.initials: FE
authors.lastname: Figueroa
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile. mkhoury@uandes.cl.|Cells for Cells, Santiago, Chile. mkhoury@uandes.cl.
authors.forename: Maroun
authors.initials: M
authors.lastname: Khoury
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008597:Menstrual Cycle / Q000097:blood*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D012313:RNA / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D012313:RNA