Exogenous bone marrow cells do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl<sub>2</sub>, despite establishment of chimaerism and cell proliferation in bone marrow and spleen

Fang, Te Chao; Otto, W; Jeffery, Rosemary; Hunt, Toby; Alison, Malcolm R.; Cook, H. Terence; Wright, Nicholas; Poulsom, Richard

doi:10.1111/j.1365-2184.2008.00546.x

Cited by 15 publications

(7 citation statements)

References 45 publications

(56 reference statements)

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“…Transdifferentiation of BM cells to functional tubular epithelium has been demonstrated previously (14,29,31); DISCUSSION however, beneficial effects of BM transplantations may have been accelerated by irradiation of mice prior to In this study, we show that an absence of the efflux pumps, P-gp or BCRP, on BM cells results in protection transplantation and kidney damage due to enhanced injury (15,30). Others showed that BM cells may improve against renal ischemia-reperfusion injury.…”

Section: Cells In Bm Of P-gp-and Bcrp-deficient Mice Possibility Of Fmentioning

confidence: 74%

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

et al. 2010

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The kidney has a high capacity to regenerate after ischemic injury via several mechanisms, one of which involves bone marrow-derived (stem) cells. The ATP binding cassette transporters, P-glycoprotein and breast cancer resistance protein, are determinants for the enriched stem and progenitor cell fraction in bone marrow. Because they are upregulated after acute kidney injury, we hypothesized that both efflux pumps may play a role in protecting against renal injury. Surprisingly, transporter-deficient mice were protected against ischemia-induced renal injury. To further study this, bone marrow from irradiated wild-type mice was reconstituted by bone marrow from wild-type, P-glycoprotein-or breast cancer resistance protein-deficient mice. Four weeks later, kidney injury was induced and its function evaluated. Significantly more bone marrow-derived cells were detected in kidneys grafted with transporter-deficient bone marrow. A gender mismatch study suggested that cell fusion of resident tubular cells with bone marrow cells was unlikely. Renal function analyses indicated an absence of renal damage following ischemia-reperfusion in animals transplanted with transporter-deficient bone marrow. When wild-type bone marrow was transplanted in breast cancer resistance protein-deficient mice this protection is lost. Furthermore, we demonstrate that transporter-deficient bone marrow contained significantly more monocytes, granulocytes, and early outgrowth endothelial progenitor cells.

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Section: Cells In Bm Of P-gp-and Bcrp-deficient Mice Possibility Of Fmentioning

confidence: 74%

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

et al. 2010

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“…These data could also explain the lack of improvement of acute tubular damage by transplanted BMCs in nonirradiated mice. 23 Even if transplanted cells were engrafted in the bone marrow, the level of donor cell engrafted was probably too low (B30%).…”

Section: Discussionmentioning

confidence: 99%

Kidney preservation by bone marrow cell transplantation in hereditary nephropathy

Yeagy

Harrison

Gubler

et al. 2011

Kidney International

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The prospect of cell-based therapy for kidney disease remains controversial despite its immense promise. We had previously shown that transplanting bone marrow and hematopoietic stem cells could generate renal cells and lead to the preservation of kidney function in a mouse model for cystinosis (Ctns(-/-)) that develops chronic kidney injury, 4 months post transplantation. Here, we determined the long-term effects of bone marrow stem cell transplantation on the kidney disease of Ctns(-/-) mice 7 to 15 months post transplantation. Transfer of bone marrow stem cells expressing a functional Ctns gene provided long-term protection to the kidney. Effective therapy, however, depended on achieving a relatively high level of donor-derived blood cell engraftment of Ctns-expressing cells, which was directly linked to the quantity of these cells within the kidney. In contrast, kidney preservation was dependent neither on renal cystine content nor on the age of the mice at the time of transplant. Most of the bone marrow-derived cells within the kidney were interstitial and not epithelial, suggesting that the mechanism involved an indirect protection of the tubules. Thus, our model may help in developing strategies to enhance the potential success of cell-based therapy for kidney injury and in understanding some of the discrepancies currently existing in the field.

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“…Of interest, a recent study showed that the administration of the MSC-derived supernatant could be sufficient to induce the beneficial effect of MSC, opening new perspectives for MSC-based therapy [38]. On the contrary, the administration of exogenous BM containing mainly HSC and a small portion of MSC, in the absence of myeloablative conditions, did not protect mice in a model of HgCl 2induced renal damage [39].…”

Section: Administration Of Msc and The Recovery From Akimentioning

confidence: 99%

Contribution of Stem Cells to Kidney Repair

Bussolati¹,

Hauser²,

Carvalhosa³

et al. 2009

CSCR

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A current explanation for development of chronic renal injury is the imbalance between injurious mechanism and regenerative repair. The possibility that stem cells contribute to the repair of glomerular and tubular damage is of great interest for basic and translational research. Endogenous bone marrow-derived stem cells have been implicated in the repair of renal tissue, although the lineage of stem cells recruited has not been determined. If endogenous bone marrow-derived stem cells repopulate injured nephrons directly or act indirectly over a paracrine/endocrine mechanism remains also controversial. Therapeutic administration of exogenous bone marrow derived stem cells in animal models of acute renal injury suggests that a stem cell-based therapy may improve the recovery of both glomerular and tubular compartments. Whereas the therapeutic benefit of sorted hematopoietic stem cells remains uncertain, several studies showed a beneficial effect of mesenchymal stem cell administration in models of acute tubular injury and of endothelial progenitors in acute glomerular injury. Recent studies demonstrate the presence of resident stem cells within the adult kidney. These cells are capable, when injected in animals with acute tubular injury, to localize to renal compartments and contribute to regeneration. This review summarizes the current literature on the physiological role of endogenous stem cells in renal regeneration and on the therapeutic potential of exogenous stem cell administration. Moreover, critical points that still need clarification, such as the homing mechanisms of stem cells to injured tissue, the secreted factors underlying the paracrine/endocrine mechanisms and the long-term behaviour of in vivo administered stem cells, are discussed.

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Exogenous bone marrow cells do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl₂, despite establishment of chimaerism and cell proliferation in bone marrow and spleen

Abstract: Exogenous BMCs do not rescue non-irradiated mice from acute renal tubular damage caused by HgCl(2), despite establishment of chimerism and cell proliferation in bone marrow and spleen.

Cited by 15 publications

References 45 publications

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

Kidney preservation by bone marrow cell transplantation in hereditary nephropathy

Contribution of Stem Cells to Kidney Repair

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Exogenous bone marrow cells do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl2, despite establishment of chimaerism and cell proliferation in bone marrow and spleen

Abstract: Exogenous BMCs do not rescue non-irradiated mice from acute renal tubular damage caused by HgCl(2), despite establishment of chimerism and cell proliferation in bone marrow and spleen.

Cited by 15 publications

References 45 publications

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

Retracted: Deficiency of Either P-Glycoprotein or Breast Cancer Resistance Protein Protect against Acute Kidney Injury

Kidney preservation by bone marrow cell transplantation in hereditary nephropathy

Contribution of Stem Cells to Kidney Repair

Contact Info

Product

Resources

About

Exogenous bone marrow cells do not rescue non‐irradiated mice from acute renal tubular damage caused by HgCl₂, despite establishment of chimaerism and cell proliferation in bone marrow and spleen