Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury

Te Chao Fang, Malcolm R. Alison, H. Terence Cook, Rosemary Jeffery, Nicholas A. Wright, Richard Poulsom

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Studies of tissue from recipients of bone marrow transplantation or organ allograft suggest that bone marrow-derived cells (BMDC) may differentiate into a variety of nonhematologic tissues, including renal tubular epithelium. The aims of this study were to examine whether BMDC contribute to recovery after acute renal injury and to assess the effects of cytokine mobilization on regeneration. Female mice (6 wk old) were lethally irradiated and transplanted with male bone marrow (BM) cells and later assigned into control, folic acid-treatment, and folic acid-treatment with granulocyte-colony stimulating factor (G-CSF), and control with G-CSF. Tritiated thymidine was given 1 h before death. Kidney sections were stained for a tubular epithelial marker, Y chromosome (in situ hybridization), periodic acid-Schiff staining, and subjected to autoradiography. Renal tubular epithelial cells in S-phase were scored as female (indigenous) or male (BM-derived). This is the first report to show that BMDC can respond by engrafting the renal tubules and undergo DNA synthesis after acute renal injury. BMDC contributed to the renal tubular epithelial cell population, although most (90%) renal tubular regeneration came from female indigenous cells. Some evidence was found for cell fusion between indigenous renal tubular cells and BMDC, but this was infrequent and the significance and consequences of cell fusion in the kidney are unresolved. G-CSF treatment nearly doubled the frequency of thymidine-labeled BM-derived tubular cells and might facilitate the recovery of renal tubular epithelium.

Original languageEnglish
Pages (from-to)1723-1732
Number of pages10
JournalJournal of the American Society of Nephrology
Volume16
Issue number6
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Folic Acid
Bone Marrow Cells
Regeneration
Kidney
Wounds and Injuries
Granulocyte Colony-Stimulating Factor
Cell Fusion
Acute Kidney Injury
Thymidine
Epithelium
Bone Marrow
Epithelial Cells
Periodic Acid
Y Chromosome
Autoradiography
Bone Marrow Transplantation
S Phase
In Situ Hybridization
Allografts
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury. / Fang, Te Chao; Alison, Malcolm R.; Cook, H. Terence; Jeffery, Rosemary; Wright, Nicholas A.; Poulsom, Richard.

In: Journal of the American Society of Nephrology, Vol. 16, No. 6, 2005, p. 1723-1732.

Research output: Contribution to journalArticle

Fang, Te Chao ; Alison, Malcolm R. ; Cook, H. Terence ; Jeffery, Rosemary ; Wright, Nicholas A. ; Poulsom, Richard. / Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury. In: Journal of the American Society of Nephrology. 2005 ; Vol. 16, No. 6. pp. 1723-1732.
@article{7dd554c261a541e9ba4ac3355cf0b80f,
title = "Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury",
abstract = "Studies of tissue from recipients of bone marrow transplantation or organ allograft suggest that bone marrow-derived cells (BMDC) may differentiate into a variety of nonhematologic tissues, including renal tubular epithelium. The aims of this study were to examine whether BMDC contribute to recovery after acute renal injury and to assess the effects of cytokine mobilization on regeneration. Female mice (6 wk old) were lethally irradiated and transplanted with male bone marrow (BM) cells and later assigned into control, folic acid-treatment, and folic acid-treatment with granulocyte-colony stimulating factor (G-CSF), and control with G-CSF. Tritiated thymidine was given 1 h before death. Kidney sections were stained for a tubular epithelial marker, Y chromosome (in situ hybridization), periodic acid-Schiff staining, and subjected to autoradiography. Renal tubular epithelial cells in S-phase were scored as female (indigenous) or male (BM-derived). This is the first report to show that BMDC can respond by engrafting the renal tubules and undergo DNA synthesis after acute renal injury. BMDC contributed to the renal tubular epithelial cell population, although most (90{\%}) renal tubular regeneration came from female indigenous cells. Some evidence was found for cell fusion between indigenous renal tubular cells and BMDC, but this was infrequent and the significance and consequences of cell fusion in the kidney are unresolved. G-CSF treatment nearly doubled the frequency of thymidine-labeled BM-derived tubular cells and might facilitate the recovery of renal tubular epithelium.",
author = "Fang, {Te Chao} and Alison, {Malcolm R.} and Cook, {H. Terence} and Rosemary Jeffery and Wright, {Nicholas A.} and Richard Poulsom",
year = "2005",
doi = "10.1681/ASN.2004121089",
language = "English",
volume = "16",
pages = "1723--1732",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "6",

}

TY - JOUR

T1 - Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury

AU - Fang, Te Chao

AU - Alison, Malcolm R.

AU - Cook, H. Terence

AU - Jeffery, Rosemary

AU - Wright, Nicholas A.

AU - Poulsom, Richard

PY - 2005

Y1 - 2005

N2 - Studies of tissue from recipients of bone marrow transplantation or organ allograft suggest that bone marrow-derived cells (BMDC) may differentiate into a variety of nonhematologic tissues, including renal tubular epithelium. The aims of this study were to examine whether BMDC contribute to recovery after acute renal injury and to assess the effects of cytokine mobilization on regeneration. Female mice (6 wk old) were lethally irradiated and transplanted with male bone marrow (BM) cells and later assigned into control, folic acid-treatment, and folic acid-treatment with granulocyte-colony stimulating factor (G-CSF), and control with G-CSF. Tritiated thymidine was given 1 h before death. Kidney sections were stained for a tubular epithelial marker, Y chromosome (in situ hybridization), periodic acid-Schiff staining, and subjected to autoradiography. Renal tubular epithelial cells in S-phase were scored as female (indigenous) or male (BM-derived). This is the first report to show that BMDC can respond by engrafting the renal tubules and undergo DNA synthesis after acute renal injury. BMDC contributed to the renal tubular epithelial cell population, although most (90%) renal tubular regeneration came from female indigenous cells. Some evidence was found for cell fusion between indigenous renal tubular cells and BMDC, but this was infrequent and the significance and consequences of cell fusion in the kidney are unresolved. G-CSF treatment nearly doubled the frequency of thymidine-labeled BM-derived tubular cells and might facilitate the recovery of renal tubular epithelium.

AB - Studies of tissue from recipients of bone marrow transplantation or organ allograft suggest that bone marrow-derived cells (BMDC) may differentiate into a variety of nonhematologic tissues, including renal tubular epithelium. The aims of this study were to examine whether BMDC contribute to recovery after acute renal injury and to assess the effects of cytokine mobilization on regeneration. Female mice (6 wk old) were lethally irradiated and transplanted with male bone marrow (BM) cells and later assigned into control, folic acid-treatment, and folic acid-treatment with granulocyte-colony stimulating factor (G-CSF), and control with G-CSF. Tritiated thymidine was given 1 h before death. Kidney sections were stained for a tubular epithelial marker, Y chromosome (in situ hybridization), periodic acid-Schiff staining, and subjected to autoradiography. Renal tubular epithelial cells in S-phase were scored as female (indigenous) or male (BM-derived). This is the first report to show that BMDC can respond by engrafting the renal tubules and undergo DNA synthesis after acute renal injury. BMDC contributed to the renal tubular epithelial cell population, although most (90%) renal tubular regeneration came from female indigenous cells. Some evidence was found for cell fusion between indigenous renal tubular cells and BMDC, but this was infrequent and the significance and consequences of cell fusion in the kidney are unresolved. G-CSF treatment nearly doubled the frequency of thymidine-labeled BM-derived tubular cells and might facilitate the recovery of renal tubular epithelium.

UR - http://www.scopus.com/inward/record.url?scp=26944431659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26944431659&partnerID=8YFLogxK

U2 - 10.1681/ASN.2004121089

DO - 10.1681/ASN.2004121089

M3 - Article

C2 - 15814835

AN - SCOPUS:26944431659

VL - 16

SP - 1723

EP - 1732

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 6

ER -