Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury

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...…”

“…Although there has been disagreement on the mechanism, MSCs have been shown to protect against both chemical (glycerol and cisplatin) and ischaemia reperfusion (IR) damage and to accelerate the repair process in rodents (see Table 1). Although initial studies suggested the potential of a high contribution of MSCs to tubular regeneration [39] or nephron formation in a specific whole embryo culture system [40], the current opinion is that only a small percentage of repaired tubular cells are BM-derived MSCs and that cell fusion may explain some results interpreted as direct replacement of epithelial cells [12]. Indeed, a recent study shows that following co-administraion of eGFP bone marrow cells with MSCs only the marrow cells engrafted into the tubules after acute renal damage [161].…”

Successful treatment of the murine model of cystinosis using bone marrow cell transplantation

“…Several studies showed that, in the setting of renal injury, transplanted MSCs can generate mesangial and tubular epithelial cells 27 and restore renal structure and function. 28,29 Others showed that MSC injections do not prevent Alport syndrome in COL4A3-deficient mice and MSCs do not differentiate into renal cells. 30 The protective effects of MSCs seem to be the result of a paracrine effect of these cells by secretion of growth factors, such as vascular endothelial growth factor and transforming growth factor-␤1, rather than cellular differentiation.…”

A Young Patient with Refractory Multiple Myeloma and Dialysis-Dependent Renal Failure has been Cured by Non-Cryopreserved Autologous Stem Cell Transplantation Followed by Live-Related Kidney Transplantation

“…Multiple preclinical studies have demonstrated that MSCs could prevent renal injury and could promote renal recovery through immunomodulation as well as release of paracrine factors and microvesicles [78]. Also, studies in animal models of acute and chronic renal failure have demonstrated the potential of MSCs to migrate into areas of inflammation, ischemia and tissue injury and due to their differentiation, regenerative and immunomodulatory properties they can ultimately improve renal function by promoting tubular proliferation and regeneration of damaged renal tissues [81][82][83][84][85].…”