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

doi:10.1002/jbm.a.34512

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 journal › Article › peer-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 language	English (US)
Pages (from-to)	2067-2074
Number of pages	8
Journal	Journal of Biomedical Materials Research - Part A
Volume	101 A
Issue number	7
DOIs	https://doi.org/10.1002/jbm.a.34512
State	Published - Jul 2013
Externally published	Yes

Keywords

CXCR4
MSC migration
SDF-1
adenovirus
lentivirus

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10.1002/jbm.a.34512

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Zwingenberger, S., Yao, Z., Jacobi, A., Vater, C., Valladares, R. D., Li, C., Nich, C., Rao, A. J., Christman, J. E., Antonios, J. K., Gibon, E., Schambach, A., Mätzig, T., Günther, K. P., Goodman, S. B., & Stiehler, M. (2013). Stem cell attraction via SDF-1α expressing fat tissue grafts. Journal of Biomedical Materials Research - Part A, 101 A(7), 2067-2074. https://doi.org/10.1002/jbm.a.34512

Zwingenberger, S, Yao, Z, Jacobi, A, Vater, C, Valladares, RD, Li, C, Nich, C, Rao, AJ, Christman, JE, Antonios, JK, Gibon, E, Schambach, A, Mätzig, T, Günther, KP, Goodman, SB & Stiehler, M 2013, 'Stem cell attraction via SDF-1α expressing fat tissue grafts', Journal of Biomedical Materials Research - Part A, vol. 101 A, no. 7, pp. 2067-2074. https://doi.org/10.1002/jbm.a.34512

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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.",

keywords = "CXCR4, MSC migration, SDF-1, adenovirus, lentivirus",

author = "Stefan Zwingenberger and Zhenyu Yao and Angela Jacobi and Corina Vater and Valladares, {Roberto D.} and Chenguang Li and Christophe Nich and Rao, {Allison J.} and Christman, {Jane E.} and Antonios, {Joseph K.} and Emmanuel Gibon and Axel Schambach and Tobias M{\"a}tzig and G{\"u}nther, {Klaus Peter} and Goodman, {Stuart B.} and Maik Stiehler",

year = "2013",

month = jul,

doi = "10.1002/jbm.a.34512",

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AU - Zwingenberger, Stefan

AU - Yao, Zhenyu

AU - Jacobi, Angela

AU - Vater, Corina

AU - Valladares, Roberto D.

AU - Li, Chenguang

AU - Nich, Christophe

AU - Rao, Allison J.

AU - Christman, Jane E.

AU - Antonios, Joseph K.

AU - Gibon, Emmanuel

AU - Schambach, Axel

AU - Mätzig, Tobias

AU - Günther, Klaus Peter

AU - Goodman, Stuart B.

AU - Stiehler, Maik

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - CXCR4

KW - MSC migration

KW - SDF-1

KW - adenovirus

KW - lentivirus

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

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