Human mesenchymal stem cells derived from adipose tissue reduce functional and tissue damage in a rat model of chronic renal failure

Abstract

Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently been reported that BM-MSCs derived from uraemic patients failed to confer functional protection in a similar model. This suggests that autologous BM-MSCs are not suitable for the treatment of CKD. In the present study, we have explored the potential of MSCs derived from adipose tissue (AD-MSCs) as an alternative source of MSCs for the treatment of CKD. We have isolated AD-MSCs and evaluated their effect on the progression of CKD. Adult male SD (Sprague-Dawley) rats subjected to 5/6 NPX (nephrectomy) received a single intravenous infusion of 0.5×10(6) AD-MSCs or MSC culture medium alone. The therapeutic effect was evaluated by plasma creatinine measurement, structural analysis and angiogenic/epitheliogenic protein expression. AD-MSCs were detected in kidney tissues from NPX animals. This group had a significant reduction in plasma creatinine levels and a lower expression of damage markers ED-1 and α-SMA (α-smooth muscle actin) (P<0.05). In addition, treated rats exhibited a higher level of epitheliogenic [Pax-2 and BMP-7 (bone morphogenetic protein 7)] and angiogenic [VEGF (vascular endothelial growth factor)] proteins. The expression of these biomarkers of regeneration was significantly related to the improvement in renal function. Although many aspects of the cell therapy for CKD remain to be investigated, we provide evidence that AD-MSCs, a less invasive and highly available source of MSCs, exert an important therapeutic effect in this pathology.

Featured Article: Induction of heme oxygenase with hemin improves pericardial adipocyte morphology and function in obese Zucker rats by enhancing proteins of regeneration

“…Importantly, these attributes of hemin were accompanied by the restoration of adipocyte morphology and improved adipocyte function as evidenced by increased adiponectin levels. Given that hypertriglyceridemia, hypercholesteromia, and excessive pericardial adiposity are major pathophysiological causes of heart failure and related cardiac complications, 8,[43][44][45][46] the suppression of hypertriglyceridemia, hypercholesteromia, and pericardial adiposity in hemin-treated ZFs, and the corresponding decline of adipocyte hypertrophy, TGF-b, osteopontin, pro-inflammatory macrophage M1 phenotype, TNF-a, IL-6, IL-1b, and 8-isoprostane, [22][23][24][25][26][27][28][29][30][31]54,[60][61][62][63] which were associated with the potentiation of the anti-inflammatory macrophage M2 phenotype, proteins of regeneration such as beta-catenin, Oct3/4, and pax2 [32][33][34] are among the multifaceted mechanisms by which the HO system restores adipocyte morphology and improved adipocyte function. Moreover, the effect of the HO system on the expression of proteins of regeneration such as Oct3/4 and pax2 is a novel mechanism unveiled by this study through which hemin may restore adipocyte morphology and function.…”

“…To investigate the mechanisms by which hemin improves pericardial adipocyte morphology, we measured the expression of proteins of regeneration such as beta-catenin, Oct3/4, and pax2 [32][33][34] in the adipose tissue. Our results indicate that the expressions of beta-catenin, Oct3/4, and pax2 in ZFs were significantly reduced as compared to the ZL control (Figure 7(a) to (c)).…”

“…1,8,9 Since osteopontin is known to promote inflammation, extracellular matrix invasion, and hypertrophy, [22][23][24][25][26][27][28][29][30][31] the effects of an upregulated HO system on the expression of osteopontin in pericardial adipocyte were assessed. Furthermore, we also investigated whether treatment with hemin improves pericardial adipocyte morphology and function by abating hypertrophy, oxidative stress, and inflammation, while concomitantly enhancing proteins of regeneration such as betacatenin, Oct3/4, and pax2 [32][33][34] in the adipose tissue. Moreover, the effects of the HO system on the expression of Oct3/4 and pax2 and osteopontin in pericardial adipose tissue have not been reported.…”

Effect of bone marrow stem cell mobilisation on the expression levels of cellular growth factors in a rat model of acute tubular necrosis

“…A number of studies have hypothesised that certain growth factors or specific hormones, including HGF, EGF and IGF-1, are able to promote this transformation process, and accelerate the differentiation of nascent epithelial cells (30)(31)(32). In addition, several scholars have demonstrated that BMSCs are able to secrete a number of cytokines, thereby promoting the proliferation and repair of the endogenous renal tubular epithelial cells (33,34).…”

A New Hypothesis: The Immunomodulatory Effects of Mesenchymal Stromal Cell Derived Extracellular Vesicles in Ischemic Kidney Injury Partly through Spleen

“…MSCs from various sources (such as bone marrow, fetal membrane and adipose) in repairing kidney injury were reported, [2][3][4] however, the potential immune rejection, adipogenic differentiation and malignant transformation events of MSCs limit our clinical use. EVs contained in the MSC's condition medium could repair variety injured organs and also could alleviate I/R injury induced AKI.…”