Haematopoietic lineage-committed bone marrow cells, but not cloned cultured mesenchymal stem cells, contribute to regeneration of renal tubular epithelium after HgCl 2 -induced acute tubular injury

• Published in: Cell proliferation 2008-08, Vol.41 (4), p.575-591
• Main Authors: Fang, T-C, Otto, W R, Rao, J, Jeffery, R, Hunt, T, Alison, M R, Cook, H T, Wright, N A, Poulsom, R
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Bone Marrow Transplantation - physiology; Cells, Cultured; Clone Cells; Epithelial Cells - drug effects; Epithelial Cells - pathology; Epithelial Cells - physiology; Female; Genes, Reporter; Hematopoiesis - physiology; In Situ Hybridization, Fluorescence; Kidney Tubules - drug effects; Kidney Tubules - injuries; Kidney Tubules - pathology; Kidney Tubules - physiology; Male; Mercuric Chloride - toxicity; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Regeneration - drug effects; Regeneration - physiology
• ISSN: 0960-7722; 1365-2184; 1365-2184
• DOI: 10.1111/j.1365-2184.2008.00545.x

Our previous studies have demonstrated that endogenous bone arrow 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. Six-week-old female mice were lethally irradiated and were transplanted with female enhanced green fluorescent protein-positive (GFP(+)), plastic on-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). 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. 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.