Stem cell attraction via SDF-1α expressing fat tissue grafts

Stefan Zwingenberger, Zhenyu Yao, Angela Jacobi, Corina Vater, Roberto D. Valladares, Chenguang Li, Christophe Nich, Allison J. Rao, Jane E. Christman, Joseph K. Antonios, Emmanuel Gibon, Axel Schambach, Tobias Mätzig, Klaus Peter Günther, Stuart B. Goodman, Maik Stiehler

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2067-2074
Number of pages8
JournalJournal of Biomedical Materials Research - Part A
Volume101 A
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • adenovirus
  • CXCR4
  • lentivirus
  • MSC migration
  • SDF-1

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