Transient canonical Wnt stimulation enriches human bone marrow mononuclear cell isolates for osteoprogenitors
Transient canonical Wnt stimulation enriches human bone marrow mononuclear cell isolates for osteoprogenitors
Activation of the canonical Wnt signaling pathway is an attractive anabolic therapeutic strategy for bone. Emerging data suggest that activation of the Wnt signaling pathway promotes bone mineral accrual in osteoporotic patients. The effect of Wnt stimulation in fracture healing is less clear as Wnt signaling has both stimulatory and inhibitory effects on osteogenesis. Here, we tested the hypothesis that transient Wnt stimulation promotes the expansion and osteogenesis of a Wnt-responsive stem cell population present in human bone marrow. Bone marrow mononuclear cells (BMMNCs) were isolated from patients undergoing hip arthroplasty and exposed to Wnt3A protein. The effect of Wnt pathway stimulation was determined by measuring the frequency of stem cells within the BMMNC populations by fluorescence-activated cell sorting and colony forming unit fibroblast (CFU-F) assays, before determining their osteogenic capacity in in vitro differentiation experiments. We found that putative skeletal stem cells in BMMNC isolates exhibited elevated Wnt pathway activity compared with the population as whole. Wnt stimulation resulted in an increase in the frequency of skeletal stem cells marked by the STRO-1(bright) /Glycophorin A(-) phenotype. Osteogenesis was elevated in stromal cell populations arising from BMMNCs transiently stimulated by Wnt3A protein, but sustained stimulation inhibited osteogenesis in a concentration-dependent manner. These results demonstrate that Wnt stimulation could be used as a therapeutic approach by transient targeting of stem cell populations during early fracture healing, but that inappropriate stimulation may prevent osteogenesis. Stem Cells 2015.
wnt signaling, marrow stromal cells/mesenchymal stem cells, osteoprogenitors, stem cells, fracture healing
1-13
Janeczek, Agnieszka A.
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Tare, Rahul S.
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Scarpa, Edoardo
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Moreno-Jimenez, Ines
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Rowland, Caroline A.
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Jenner, Dominic
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Newman, Tracey A.
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Oreffo, Richard O.C.
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Evans, Nicholas D.
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Janeczek, Agnieszka A.
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Tare, Rahul S.
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Scarpa, Edoardo
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Moreno-Jimenez, Ines
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Rowland, Caroline A.
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Jenner, Dominic
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Newman, Tracey A.
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Oreffo, Richard O.C.
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Evans, Nicholas D.
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Janeczek, Agnieszka A., Tare, Rahul S., Scarpa, Edoardo, Moreno-Jimenez, Ines, Rowland, Caroline A., Jenner, Dominic, Newman, Tracey A., Oreffo, Richard O.C. and Evans, Nicholas D.
(2015)
Transient canonical Wnt stimulation enriches human bone marrow mononuclear cell isolates for osteoprogenitors.
Stem Cells, .
(doi:10.1002/stem.2241).
(PMID:26573091)
Abstract
Activation of the canonical Wnt signaling pathway is an attractive anabolic therapeutic strategy for bone. Emerging data suggest that activation of the Wnt signaling pathway promotes bone mineral accrual in osteoporotic patients. The effect of Wnt stimulation in fracture healing is less clear as Wnt signaling has both stimulatory and inhibitory effects on osteogenesis. Here, we tested the hypothesis that transient Wnt stimulation promotes the expansion and osteogenesis of a Wnt-responsive stem cell population present in human bone marrow. Bone marrow mononuclear cells (BMMNCs) were isolated from patients undergoing hip arthroplasty and exposed to Wnt3A protein. The effect of Wnt pathway stimulation was determined by measuring the frequency of stem cells within the BMMNC populations by fluorescence-activated cell sorting and colony forming unit fibroblast (CFU-F) assays, before determining their osteogenic capacity in in vitro differentiation experiments. We found that putative skeletal stem cells in BMMNC isolates exhibited elevated Wnt pathway activity compared with the population as whole. Wnt stimulation resulted in an increase in the frequency of skeletal stem cells marked by the STRO-1(bright) /Glycophorin A(-) phenotype. Osteogenesis was elevated in stromal cell populations arising from BMMNCs transiently stimulated by Wnt3A protein, but sustained stimulation inhibited osteogenesis in a concentration-dependent manner. These results demonstrate that Wnt stimulation could be used as a therapeutic approach by transient targeting of stem cell populations during early fracture healing, but that inappropriate stimulation may prevent osteogenesis. Stem Cells 2015.
Text
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Accepted/In Press date: 1 October 2015
e-pub ahead of print date: 17 November 2015
Keywords:
wnt signaling, marrow stromal cells/mesenchymal stem cells, osteoprogenitors, stem cells, fracture healing
Organisations:
Bioengineering Group, Engineering Science Unit, Human Development & Health
Identifiers
Local EPrints ID: 386694
URI: http://eprints.soton.ac.uk/id/eprint/386694
ISSN: 1066-5099
PURE UUID: ce905252-36f0-4222-b66e-5f83d466a2a2
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Date deposited: 03 Feb 2016 14:19
Last modified: 15 Mar 2024 03:37
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Contributors
Author:
Agnieszka A. Janeczek
Author:
Edoardo Scarpa
Author:
Ines Moreno-Jimenez
Author:
Caroline A. Rowland
Author:
Dominic Jenner
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