Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification

Shawn J. Loder, Shailesh Agarwal, Michael T. Chung, David Cholok, Charles Hwang, Noelle Visser, Kaetlin Vasquez, Michael Sorkin, Joe Habbouche, Hsiao H. Sung, Joshua Peterson, David Fireman, Kavitha Ranganathan, Christopher Breuler, Caitlin Priest, John Li, Xue Bai, Shuli Li, Paul S. Cederna, Benjamin Levi

Research output: Contribution to journalArticle

Abstract

Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein–positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.

Original languageEnglish (US)
Pages (from-to)2464-2473
Number of pages10
JournalAmerican Journal of Pathology
Volume188
Issue number11
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

Fingerprint

Heterotopic Ossification
Population
Wounds and Injuries
Parabiosis
Achilles Tendon
Luciferases
Mesenchymal Stromal Cells
Immune System

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Loder, S. J., Agarwal, S., Chung, M. T., Cholok, D., Hwang, C., Visser, N., ... Levi, B. (2018). Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification. American Journal of Pathology, 188(11), 2464-2473. https://doi.org/10.1016/j.ajpath.2018.07.014

Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification. / Loder, Shawn J.; Agarwal, Shailesh; Chung, Michael T.; Cholok, David; Hwang, Charles; Visser, Noelle; Vasquez, Kaetlin; Sorkin, Michael; Habbouche, Joe; Sung, Hsiao H.; Peterson, Joshua; Fireman, David; Ranganathan, Kavitha; Breuler, Christopher; Priest, Caitlin; Li, John; Bai, Xue; Li, Shuli; Cederna, Paul S.; Levi, Benjamin.

In: American Journal of Pathology, Vol. 188, No. 11, 01.11.2018, p. 2464-2473.

Research output: Contribution to journalArticle

Loder, SJ, Agarwal, S, Chung, MT, Cholok, D, Hwang, C, Visser, N, Vasquez, K, Sorkin, M, Habbouche, J, Sung, HH, Peterson, J, Fireman, D, Ranganathan, K, Breuler, C, Priest, C, Li, J, Bai, X, Li, S, Cederna, PS & Levi, B 2018, 'Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification', American Journal of Pathology, vol. 188, no. 11, pp. 2464-2473. https://doi.org/10.1016/j.ajpath.2018.07.014
Loder, Shawn J. ; Agarwal, Shailesh ; Chung, Michael T. ; Cholok, David ; Hwang, Charles ; Visser, Noelle ; Vasquez, Kaetlin ; Sorkin, Michael ; Habbouche, Joe ; Sung, Hsiao H. ; Peterson, Joshua ; Fireman, David ; Ranganathan, Kavitha ; Breuler, Christopher ; Priest, Caitlin ; Li, John ; Bai, Xue ; Li, Shuli ; Cederna, Paul S. ; Levi, Benjamin. / Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification. In: American Journal of Pathology. 2018 ; Vol. 188, No. 11. pp. 2464-2473.
@article{3679e6740fe34516aca4b9bd3488689d,
title = "Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification",
abstract = "Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein–positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.",
author = "Loder, {Shawn J.} and Shailesh Agarwal and Chung, {Michael T.} and David Cholok and Charles Hwang and Noelle Visser and Kaetlin Vasquez and Michael Sorkin and Joe Habbouche and Sung, {Hsiao H.} and Joshua Peterson and David Fireman and Kavitha Ranganathan and Christopher Breuler and Caitlin Priest and John Li and Xue Bai and Shuli Li and Cederna, {Paul S.} and Benjamin Levi",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.ajpath.2018.07.014",
language = "English (US)",
volume = "188",
pages = "2464--2473",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification

AU - Loder, Shawn J.

AU - Agarwal, Shailesh

AU - Chung, Michael T.

AU - Cholok, David

AU - Hwang, Charles

AU - Visser, Noelle

AU - Vasquez, Kaetlin

AU - Sorkin, Michael

AU - Habbouche, Joe

AU - Sung, Hsiao H.

AU - Peterson, Joshua

AU - Fireman, David

AU - Ranganathan, Kavitha

AU - Breuler, Christopher

AU - Priest, Caitlin

AU - Li, John

AU - Bai, Xue

AU - Li, Shuli

AU - Cederna, Paul S.

AU - Levi, Benjamin

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein–positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.

AB - Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein–positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.

UR - http://www.scopus.com/inward/record.url?scp=85055170535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055170535&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2018.07.014

DO - 10.1016/j.ajpath.2018.07.014

M3 - Article

C2 - 30142335

AN - SCOPUS:85055170535

VL - 188

SP - 2464

EP - 2473

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 11

ER -