Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction

Stacy T. Tanaka, Magaly Martinez-Ferrer, John H. Makari, Marcia L. Wills, John C. Thomas, Mark C. Adams, John W. Brock, John C. Pope IV, Neil A. Bhowmick

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model. Materials and Methods: We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting. Results: Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells. Conclusions: Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy.

Original languageEnglish (US)
Pages (from-to)1769-1774
Number of pages6
JournalJournal of Urology
Volume182
Issue number4 SUPPL.
DOIs
StatePublished - Oct 2009

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Urinary Bladder Neck Obstruction
Bone Marrow Cells
Urinary Bladder
Fibrosis
Chemokine CCL2
Urodynamics
Green Fluorescent Proteins
Kidney Diseases
Reverse Transcriptase Polymerase Chain Reaction
Mesenchymal Stromal Cells
Chemokines
Epidermal Growth Factor Receptor
Hypertrophy
Transgenic Mice
Lung Diseases
Heart Diseases
Flow Cytometry
Collagen
Bone Marrow
Immunohistochemistry

Keywords

  • Animal use alternatives
  • Bone marrow cells
  • Chemokines
  • Fibrosis
  • Urinary bladder neck obstruction

ASJC Scopus subject areas

  • Urology

Cite this

Tanaka, S. T., Martinez-Ferrer, M., Makari, J. H., Wills, M. L., Thomas, J. C., Adams, M. C., ... Bhowmick, N. A. (2009). Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction. Journal of Urology, 182(4 SUPPL.), 1769-1774. https://doi.org/10.1016/j.juro.2009.02.081

Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction. / Tanaka, Stacy T.; Martinez-Ferrer, Magaly; Makari, John H.; Wills, Marcia L.; Thomas, John C.; Adams, Mark C.; Brock, John W.; Pope IV, John C.; Bhowmick, Neil A.

In: Journal of Urology, Vol. 182, No. 4 SUPPL., 10.2009, p. 1769-1774.

Research output: Contribution to journalArticle

Tanaka, ST, Martinez-Ferrer, M, Makari, JH, Wills, ML, Thomas, JC, Adams, MC, Brock, JW, Pope IV, JC & Bhowmick, NA 2009, 'Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction', Journal of Urology, vol. 182, no. 4 SUPPL., pp. 1769-1774. https://doi.org/10.1016/j.juro.2009.02.081
Tanaka, Stacy T. ; Martinez-Ferrer, Magaly ; Makari, John H. ; Wills, Marcia L. ; Thomas, John C. ; Adams, Mark C. ; Brock, John W. ; Pope IV, John C. ; Bhowmick, Neil A. / Recruitment of bone marrow derived cells to the bladder after bladder outlet obstruction. In: Journal of Urology. 2009 ; Vol. 182, No. 4 SUPPL. pp. 1769-1774.
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abstract = "Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model. Materials and Methods: We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting. Results: Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells. Conclusions: Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy.",
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AU - Martinez-Ferrer, Magaly

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AU - Wills, Marcia L.

AU - Thomas, John C.

AU - Adams, Mark C.

AU - Brock, John W.

AU - Pope IV, John C.

AU - Bhowmick, Neil A.

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N2 - Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model. Materials and Methods: We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting. Results: Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells. Conclusions: Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy.

AB - Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs. To our knowledge we present the first report of bone marrow derived cell recruitment to the bladder in a murine bladder outlet obstruction model. Materials and Methods: We lethally irradiated WT female mice and reconstituted their bone marrow using fetal liver cells from transgenic mice ubiquitously expressing green fluorescent protein. Periurethral collagen injection was used for bladder outlet obstruction. Obstruction was assessed by urodynamics, and bladder and kidney histological changes. Bladders were harvested 1 to 12 weeks after bladder outlet obstruction and compared to those in nonobstructed controls. The chemokine CCL2 was compared between obstructed and nonobstructed mice with reverse transcriptase-polymerase chain reaction. Green fluorescent protein expressing bone marrow derived cells were identified with immunohistochemistry and fluorescence activated cell sorting. Results: Bladders showed histological and urodynamic changes consistent with obstruction. CCL2 induction increased after obstruction compared to that in controls. After obstruction bone marrow derived cells were present in the urothelial and stromal layers. Activated epidermal growth factor receptor was found in cells associated with bone marrow derived cells. Conclusions: Bone marrow derived cells are recruited to the bladder by bladder outlet obstruction and are present in the urothelial and stromal layers. Stromal bone marrow derived cells may have a role in hypertrophy and fibrosis. Further study of the recruitment and function of bone marrow derived cells in the bladder may provide potential targets for antifibrotic therapy.

KW - Animal use alternatives

KW - Bone marrow cells

KW - Chemokines

KW - Fibrosis

KW - Urinary bladder neck obstruction

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