Intrarenal cells, not bone marrow–derived cells, are the major source for regeneration in postischemic kidney

Stem cell options for kidney disease

“…Furthermore, ex vivo manipulation of macrophages using specific cytokines confirmed that classically activated, M1 macrophages worsen chronic inflammatory adriamycin nephropathy, whereas alternatively activated M2 macrophages reduce histological disruption and functional injury [36]. Of note, in the heart Camargo et al [37] have [39] Glycerol-induced ARF (mouse) MSCs Enhanced tubular proliferation [68] IR (rat) Papilla LRCs Proliferation and incorporation [149] IR (mouse) Bone marrow No functional improvement, intrarenal cells are the main source of repopulating cell during repair [22] Folic acid-induced acute tubular injury (mouse) Bone marrow Intrinsic tubular cell proliferation accounts for repair after damage [150] Folic acid-induced acute tubular injury (mouse) Bone marrow 10% incorporation in tubules and G-CSF doubles this rate [151] IR (rat) MSCs Improved renal function and less injury [152] Cisplatin-induced renal failure (mouse) MSCs Accelerated tubular proliferation [153] UUO (mouse) Bone marrow macrophages Reduced renal fibrosis [41] IR (rat) MSCs Improved renal function, increased proliferation and decreased apoptosis [84] IR (rat) rKS56 (S3 segment outgrowth) Replace tubular and improve function [80] Glycerol-induced tubulonecrosis (mouse) Human CD133 + cells Homing and tubular integration [66] UUO (rat) Label-retaining cells (LRC) Proliferates, migrates and transdifferentiates into fibroblast-like cells [27] Cisplatin-induced renal failure (mouse) G-CSF ± M-CSF Improvement in renal function and prevention of renal tubular injury [154] Anti-Thy1.1 GN (rat) MSCs Increased glomerular proliferation and reduction in proteinuria [53] Col4α3 deficiency (mouse) MSCs Prevented loss of peritubular capillaries and reduced fibrosis but no increase in function or survival [24] Col4α3 deficiency (mouse) Bone marrow Partial restoration of expression of the type IV collagen α3 chain, improved histology and function [25] Col4α3 deficiency (mouse) MSCs Improved function and glomerular scarring and interstitial fibrosis reduced [155] UUO (mouse) BM Instertitial BM-derived cells do not contribute significantly to collagen synthesis after damage [74] Adriamycin-nephropathy (mouse) Renal side population Functional amprovement but very low rate of engraftment. [78] IR (rat) Multipotent renal progenitor cells In vivo epithelial differentiation, no difference on renal function [67] Cultured met...…”

“…While it was suggested that there was evidence of cells integrating into a variety of renal cellular compartments, the degree of engraftment and the distinction between functional transdifferentiation and fusion was slower to be examined. Lin et al [21] and Duffield et al [22] finally concluded that the contribution of bone marrow-derived cells to the kidney was relatively low (0.06-8%). Futhermore, Held et al [23] have shown that a 20-50% cell fusion could be induced between bone marrow-derived cells and renal tubular cells under conditions of chronic renal damage.…”

“…There is also evidence that such repair occurs independently of any contribution by exogenous stem cells [22]. In BM-transplanted mice, whilst the majority of transplanted cells ended up as interstitial cells, somewhere between 4% and 11% of these cells do appear to contribute to renal epithelium [21,63]. However, >89% of proliferating tubular epithelial cells were host-derived cells, suggesting that intrarenal cells are the main source of renal repair.…”

Pericytes and Perivascular Fibroblasts Are the Primary Source of Collagen-Producing Cells in Obstructive Fibrosis of the Kidney

“…1 Derivation of myofibroblasts from bone marrow-derived CD34ϩ circulating cells known as fibrocytes has been proposed in several studies, and conflicting data have been published suggesting that a separate population of bone marrow-derived myofibroblasts contribute to interstitial fibroblasts in the kidney. [2][3][4] Injured epithelial cells undergoing epithelial to mesenchymal transition (EMT) have been proposed to contribute to kidney myofibroblasts as well, with some studies suggesting epithelial cells are the major source of fibroblasts in the kidney and elsewhere. 5,6 We have recently reported using robust, reproducible genetic fate mapping techniques in vivo that epithelial cells make no significant contribution to myofibroblasts in mouse kidney fibrosis (Humphreys et al, manuscript submitted for publication).…”

A potential biomarker of androgen exposure in European bullhead (Cottus sp.) kidney

“…Concerning the head kidney, as for other fish species, this compartment is lacking in nephrons and largely composed of haematopoietic and lymphopoietic tissues. The trunk kidney of the bullhead had few nephrons (25 ± 5%) and much immune tissue (75 ± 5 %) which was not limited to the area around the renal tubules (Lin et al 2005;Whyte 2007). This observation is not in accordance with histological descriptions of the trunk kidney structure in other fish species such as the stickleback, which exhibits haematopoetic tissue and is located in the interstitial region surrounding renal tubules (Mourier 1970).…”