title: Stem cell attraction via SDF-1α expressing fat tissue grafts.
abstract: Mesenchymal stromal cell (MSCs) are key cellular components for site-specific tissue regeneration. The chemokine stromal derived factor 1 alpha (SDF-1α) is known to attract stem cells via the C-X-C chemokine receptor-4 (CXCR4) receptor. The aim of the study was to develop a model for stem cell attraction using SDF-1α overexpressing fat tissue grafts. Murine MSCs were lentiviral transduced to express the genes for enhanced green fluorescent protein, firefly luciferace, and human CXCR4 (hCXCR4). Murine fat tissue was adenoviral transduced to express SDF-1α and red fluorescent protein transgenes. MSCs were cultured on transwells with SDF-1α containing supernatants from transduced fat tissue. The numbers of migrated MSCs in four groups (with hCXCR4 positive (+) or hCXCR4 negative (-) MSCs with or without SDF-1α containing supernatant) were investigated. After 36 h of culture, 9025 ± 925 cells migrated through the membrane of the transwells in group 1 (CXCR4+/SDF-1α+), 4817 ± 940 cells in group 2 (CXCR4-/SDF-1α+), 2050 ± 766 cells in group 3 (CXCR4+/SDF-1α-), and 2108 ± 426 cells in group 4 (CXCR4-/SDF-1α-). Both, the presence of SDF-1α and the expression of hCXCR4 significantly increased the migration rates (p < 0.0001). MSCs overexpressing the CXCR4 receptor by lentiviral transduction are highly attracted by medium from SDF-1α expressing fat tissue in vitro. Thus, SDF-1α activated tissue grafts may be a strategy to enhance site-specific musculoskeletal tissue regeneration.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California, USA. stefan.zwingenberger@uniklinikum-dresden.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zwingenberger
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Angela
authors.initials: A
authors.lastname: Jacobi
authors.forename: Corina
authors.initials: C
authors.lastname: Vater
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Valladares
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.forename: Christophe
authors.initials: C
authors.lastname: Nich
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Rao
authors.forename: Jane E
authors.initials: JE
authors.lastname: Christman
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Antonios
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gibon
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Tobias
authors.initials: T
authors.lastname: Mätzig
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Günther
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: Maik
authors.initials: M
authors.lastname: Stiehler
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000637:transplantation*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D000229:Dependovirus / Q000235:genetics; D005434:Flow Cytometry; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins