Mesenchymal stem cell expression of stromal cell-derived factor-1β augments bone formation in a model of local regenerative therapy

Samuel Herberg, Galina Kondrikova, Khaled A. Hussein, Maribeth H Johnson, Mohammed Elsayed Elsalanty, Xing Ming Shi, Mark W Hamrick, Carlos M Isales, William D Hill

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1β), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1β enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1β augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1β, expressed at high levels in Tet-Off-SDF-1β BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo μCT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1β to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1β expression in vivo. In conclusion, SDF-1β provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.

Original languageEnglish (US)
Pages (from-to)174-184
Number of pages11
JournalJournal of Orthopaedic Research
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Chemokine CXCL12
Mesenchymal Stromal Cells
Osteogenesis
Bone Marrow
Tetracycline
Therapeutics
Bone and Bones
Mesenchymal Stem Cell Transplantation
Therapeutic Uses
Cell Differentiation
Transplantation

Keywords

  • BMSCs
  • Bone formation
  • Irradiation
  • SDF-1/CXCL12
  • Stem cell transplantation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

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title = "Mesenchymal stem cell expression of stromal cell-derived factor-1β augments bone formation in a model of local regenerative therapy",
abstract = "Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1β), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1β enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1β augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1β, expressed at high levels in Tet-Off-SDF-1β BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo μCT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1β to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1β expression in vivo. In conclusion, SDF-1β provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.",
keywords = "BMSCs, Bone formation, Irradiation, SDF-1/CXCL12, Stem cell transplantation",
author = "Samuel Herberg and Galina Kondrikova and Hussein, {Khaled A.} and Johnson, {Maribeth H} and Elsalanty, {Mohammed Elsayed} and Shi, {Xing Ming} and Hamrick, {Mark W} and Isales, {Carlos M} and Hill, {William D}",
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T1 - Mesenchymal stem cell expression of stromal cell-derived factor-1β augments bone formation in a model of local regenerative therapy

AU - Herberg, Samuel

AU - Kondrikova, Galina

AU - Hussein, Khaled A.

AU - Johnson, Maribeth H

AU - Elsalanty, Mohammed Elsayed

AU - Shi, Xing Ming

AU - Hamrick, Mark W

AU - Isales, Carlos M

AU - Hill, William D

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1β), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1β enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1β augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1β, expressed at high levels in Tet-Off-SDF-1β BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo μCT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1β to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1β expression in vivo. In conclusion, SDF-1β provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.

AB - Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1β), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1β enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1β augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1β, expressed at high levels in Tet-Off-SDF-1β BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo μCT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1β to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1β expression in vivo. In conclusion, SDF-1β provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols.

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KW - Irradiation

KW - SDF-1/CXCL12

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