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 E. Elsalanty, Xingming Shi, Mark W. Hamrick, Carlos M. Isales, William D. Hill

Research output: Contribution to journalArticle

6 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 E.} and Xingming Shi and Hamrick, {Mark W.} and Isales, {Carlos M.} and Hill, {William D.}",
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TY - JOUR

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 E.

AU - Shi, Xingming

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.

KW - BMSCs

KW - Bone formation

KW - Irradiation

KW - SDF-1/CXCL12

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