Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl2-induced acute tubular injury

T. C. Fang, W. R. Otto, J. Rao, R. Jeffery, T. Hunt, M. R. Alison, H. T. Cook, N. A. Wright, R. Poulsom

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objective: Our previous studies have demonstrated that endogenous bone marrow cells (BMCs) contribute to renal tubular regeneration after acute tubular injury. The aim of this study was to examine which fraction of BMCs, haematopoietic lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective. Materials and methods: Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP+), plastic non-adherent marrow cells (as a source of HLMCs) plus cloned cultured male GFP- MSCs. Four weeks later, they were assigned into two groups: control mice with vehicle treatment and mice treated with HgCl2. Tritiated thymidine was given 1 h before animal killing which occurred at intervals over 2 weeks. Kidney sections were stained for a tubular epithelial marker, cell origin indicated by GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid-Schiff staining was performed, and samples were subjected to autoradiography. One thousand consecutive renal tubular epithelial cells per mouse, in S phase, were scored as either female (indigenous) GFP+ (HLMC-derived) or male (MSC-derived). Results: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal tubules and were able to undergo DNA synthesis after acute renal injury. A few MSCs were detected in the renal interstitium, but their importance needs to be further explored. Conclusion: Haematopoietic lineage marrow cells, but not cloned cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal tubular cells, but also in repair after tubular injury.

Original languageEnglish
Pages (from-to)575-591
Number of pages17
JournalCell Proliferation
Volume41
Issue number4
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

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Mercuric Chloride
Mesenchymal Stromal Cells
Bone Marrow Cells
Regeneration
Epithelium
Bone Marrow
Kidney
Wounds and Injuries
Epithelial Cells
Periodic Acid
Y Chromosome
Cell Lineage
Autoradiography
Tears
S Phase
Acute Kidney Injury
Thymidine
Plastics
In Situ Hybridization
Spleen

ASJC Scopus subject areas

  • Cell Biology

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Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl2-induced acute tubular injury. / Fang, T. C.; Otto, W. R.; Rao, J.; Jeffery, R.; Hunt, T.; Alison, M. R.; Cook, H. T.; Wright, N. A.; Poulsom, R.

In: Cell Proliferation, Vol. 41, No. 4, 08.2008, p. 575-591.

Research output: Contribution to journalArticle

Fang, T. C. ; Otto, W. R. ; Rao, J. ; Jeffery, R. ; Hunt, T. ; Alison, M. R. ; Cook, H. T. ; Wright, N. A. ; Poulsom, R. / Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl2-induced acute tubular injury. In: Cell Proliferation. 2008 ; Vol. 41, No. 4. pp. 575-591.
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abstract = "Objective: Our previous studies have demonstrated that endogenous bone marrow cells (BMCs) contribute to renal tubular regeneration after acute tubular injury. The aim of this study was to examine which fraction of BMCs, haematopoietic lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective. Materials and methods: Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP+), plastic non-adherent marrow cells (as a source of HLMCs) plus cloned cultured male GFP- MSCs. Four weeks later, they were assigned into two groups: control mice with vehicle treatment and mice treated with HgCl2. Tritiated thymidine was given 1 h before animal killing which occurred at intervals over 2 weeks. Kidney sections were stained for a tubular epithelial marker, cell origin indicated by GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid-Schiff staining was performed, and samples were subjected to autoradiography. One thousand consecutive renal tubular epithelial cells per mouse, in S phase, were scored as either female (indigenous) GFP+ (HLMC-derived) or male (MSC-derived). Results: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal tubules and were able to undergo DNA synthesis after acute renal injury. A few MSCs were detected in the renal interstitium, but their importance needs to be further explored. Conclusion: Haematopoietic lineage marrow cells, but not cloned cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal tubular cells, but also in repair after tubular injury.",
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AU - Fang, T. C.

AU - Otto, W. R.

AU - Rao, J.

AU - Jeffery, R.

AU - Hunt, T.

AU - Alison, M. R.

AU - Cook, H. T.

AU - Wright, N. A.

AU - Poulsom, R.

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N2 - Objective: Our previous studies have demonstrated that endogenous bone marrow cells (BMCs) contribute to renal tubular regeneration after acute tubular injury. The aim of this study was to examine which fraction of BMCs, haematopoietic lineage marrow cells (HLMCs) or mesenchymal stem cells (MSCs), are effective. Materials and methods: Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP+), plastic non-adherent marrow cells (as a source of HLMCs) plus cloned cultured male GFP- MSCs. Four weeks later, they were assigned into two groups: control mice with vehicle treatment and mice treated with HgCl2. Tritiated thymidine was given 1 h before animal killing which occurred at intervals over 2 weeks. Kidney sections were stained for a tubular epithelial marker, cell origin indicated by GFP immunohistochemistry or Y chromosome in situ hybridization; periodic acid-Schiff staining was performed, and samples were subjected to autoradiography. One thousand consecutive renal tubular epithelial cells per mouse, in S phase, were scored as either female (indigenous) GFP+ (HLMC-derived) or male (MSC-derived). Results: Haematopoietic lineage marrow cells and MSCs stably engrafted into bone marrow and spleen, but only HLMC-derived cells, not MSCs, were found in the renal tubules and were able to undergo DNA synthesis after acute renal injury. A few MSCs were detected in the renal interstitium, but their importance needs to be further explored. Conclusion: Haematopoietic lineage marrow cells, but not cloned cultured MSCs, can play a role not only in normal wear-and-tear turnover of renal tubular cells, but also in repair after tubular injury.

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