Cells Derived from Young Bone Marrow Alleviate Renal Aging

Abstract

Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less ␤-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show ␤-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor ␤. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

The Aging Kidney Phenotype and Systemically Derived Stem Cells

“…2 The experiments from the laboratory of Fogo and colleagues 17 in this issue of JASN extend previous studies showing both that the aging phenotype to young mice could be transferred by bone marrow transplantation (BMT) and that at least some of the glomerular changes in aging could be reduced. 18 The current study addresses this problem by using male donors and examining recipient kidneys for the Y chromosome.…”

“…Namely, is the nephrology field ready to address kidney aging experimentally or clinically using bone marrow transplantation? A note of caution is that the data from the current study 17 and from the others cited above suggest that normal aging is associated with phenotypic changes in bone marrow cells, and this could also apply to stem cells isolated from other adult tissues. Apart from this issue, one cannot utilize stem cells without selection for the targeted organ without the risk of tumor development.…”

“…18 The current study addresses this problem by using male donors and examining recipient kidneys for the Y chromosome. 17 Although some previous studies did not include lineage tracing, mesangial cells isolated from the glomeruli of young recipients of marrow transplants from old mice had a similar phenotype to mesangial cells isolated from aging mice. 18 More convincing evidence of the transfer of a specific sclerosis-prone phenotype and genotype was provided in earlier studies from the same laboratory, in which the glomerular phenotype depended on the genotype delivered with transplanted bone marrow and the number of cells with that phenotype that repopulated the glomeruli.…”

Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway

“…2B). S100A4 (also known as Mts1 and FSP1) is a specific fibroblast protein, and may function in motility, invasion, and tubulin polymerization [26]. Tjp1 is a scaffolding protein of the membrane-associated guanylate kinase family associated with tight junctions [27].…”

Bone Marrow Rejuvenation

“…10 Therefore, bone marrow transplantation is considered for the treatment of a variety of other diseases. Bone marrow rejuvenation reduced ischemic brain injury in aged rats 11 and alleviated renal aging in old mice, 12 aside from the treatment of age-related endothelial dysfunction. 13 Bone marrow transplantation seems as if the dawn of the night to refractory aging related endothelial dysfunction, but it still had to face many challenges for clinical application.…”