Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model

Chrisoula A. Toupadakis; Jennifer L. Granick; Myrrh Sagy; Alice Wong; Ehssan Ghassemi; Dai Jung Chung; Dori L. Borjesson; Clare E. Yellowley

doi:10.1016/j.jcyt.2013.05.004

Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model

Chrisoula A. Toupadakis, Jennifer L. Granick, Myrrh Sagy, Alice Wong, Ehssan Ghassemi, Dai Jung Chung, Dori L. Borjesson, Clare E. Yellowley

Veterinary Clinical Sciences

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Background aims: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. Methods: A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography. Results: AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84. Conclusions: Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.

Original language	English (US)
Pages (from-to)	1136-1147
Number of pages	12
Journal	Cytotherapy
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.jcyt.2013.05.004
State	Published - Sep 2013

Bibliographical note

Funding Information:
We thank Carol Oxford at the University of California, Davis Flow Cytometry Shared Resource for technical assistance and Dr Peta Hitchens for assistance with statistical analyses. This work was funded by Project S-10-62Y supported by the AO Foundation , National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R21AR061604 (CEY) and private grant from Dick and Carolyn Randall .

Keywords

AMD3100
Bone regeneration
Fracture repair
Mobilization
Stem cells

Publisher link

10.1016/j.jcyt.2013.05.004

Find It

Find It at U of M Libraries

Cite this

@article{3a29d5c2b4b341c7b18cccbf290c488f,

title = "Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model",

abstract = "Background aims: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. Methods: A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography. Results: AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84. Conclusions: Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.",

keywords = "AMD3100, Bone regeneration, Fracture repair, Mobilization, Stem cells",

author = "Toupadakis, {Chrisoula A.} and Granick, {Jennifer L.} and Myrrh Sagy and Alice Wong and Ehssan Ghassemi and Chung, {Dai Jung} and Borjesson, {Dori L.} and Yellowley, {Clare E.}",

note = "Funding Information: We thank Carol Oxford at the University of California, Davis Flow Cytometry Shared Resource for technical assistance and Dr Peta Hitchens for assistance with statistical analyses. This work was funded by Project S-10-62Y supported by the AO Foundation , National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R21AR061604 (CEY) and private grant from Dick and Carolyn Randall . ",

year = "2013",

month = sep,

doi = "10.1016/j.jcyt.2013.05.004",

language = "English (US)",

volume = "15",

pages = "1136--1147",

journal = "Cytotherapy",

issn = "1465-3249",

publisher = "Elsevier B.V.",

number = "9",

}

TY - JOUR

T1 - Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model

AU - Toupadakis, Chrisoula A.

AU - Granick, Jennifer L.

AU - Sagy, Myrrh

AU - Wong, Alice

AU - Ghassemi, Ehssan

AU - Chung, Dai Jung

AU - Borjesson, Dori L.

AU - Yellowley, Clare E.

N1 - Funding Information: We thank Carol Oxford at the University of California, Davis Flow Cytometry Shared Resource for technical assistance and Dr Peta Hitchens for assistance with statistical analyses. This work was funded by Project S-10-62Y supported by the AO Foundation , National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R21AR061604 (CEY) and private grant from Dick and Carolyn Randall .

PY - 2013/9

Y1 - 2013/9

N2 - Background aims: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. Methods: A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography. Results: AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84. Conclusions: Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.

AB - Background aims: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. Methods: A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography. Results: AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84. Conclusions: Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.

KW - AMD3100

KW - Bone regeneration

KW - Fracture repair

KW - Mobilization

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=84881113549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881113549&partnerID=8YFLogxK

U2 - 10.1016/j.jcyt.2013.05.004

DO - 10.1016/j.jcyt.2013.05.004

M3 - Article

C2 - 23831362

AN - SCOPUS:84881113549

SN - 1465-3249

VL - 15

SP - 1136

EP - 1147

JO - Cytotherapy

JF - Cytotherapy

IS - 9

ER -

Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this