scholarly journals Treatment with Mesenchymal Stem Cells Improves Renovascular Hypertension and Preserves the Ability of the Contralateral Kidney to Excrete Sodium

2019 ◽  
Vol 44 (6) ◽  
pp. 1404-1415 ◽  
Author(s):  
Vanessa Araujo Varela ◽  
Elizabeth B. Oliveira-Sales ◽  
Edgar Maquigussa ◽  
Fernanda T. Borges ◽  
Pedro P. Gattai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Renovascular Hypertension ◽  
Urinary Flow ◽  
Gene Expressions ◽  
Renal Deterioration ◽  
Contralateral Kidney ◽  
Sodium Transporters ◽  
Sodium Loss

Background: Mesenchymal stem cells (MSC) improve renal function and renovascular hypertension in the 2-kidney 1-clip model (2K-1C). While MSC play an immunomodulatory role, induce neoangiogenesis, and reduce fibrosis, they do not correct sodium loss by the contra­lateral kidney. Objectives: We investigated the tubular function of both stenotic and contralateral kidneys and the effect of MSC treatment by evaluating diuresis, natriuresis, and the expression of the main water and sodium transporters. Method: Adult Wistar rats were allocated into four groups: control (CT), CT+MSC, 2K-1C, and 2K-1C+MSC. MSC (2 × 105) were infused through the tail vein 3 and 5 weeks after clipping. Systolic blood pressure (SBP) was monitored weekly by plethysmography. Six weeks after clipping, 24-hour urine and blood samples were collected for biochemical analysis. Gene expression of the Na/H exchanger-3, epithelial sodium channel, Na/K-ATPase, Na/K/2Cl cotransporter, and aquaporins 1 and 2 (AQP1 and AQP2) were analyzed by RT-PCR. Intrarenal distribution of AQP1 and AQP2 was analyzed by immunohistochemistry. Results: In hypertensive 2K-1C animals, MSC prevented additional increases in BP. AQP1, but not AQP2, was suppressed in the contralateral kidney, resulting in significant increase in urinary flow rate and sodium excretion. Gene expressions of sodium transporters were similar in both kidneys, suggesting that the high perfusing pressure in the contralateral kidney was responsible for increased natriuresis. Contralateral hypertensive kidney showed signs of renal deterioration with lower GFR in spite of normal RPF levels. Conclusions: MSC treatment improved renal function and enhanced the ability of the contralateral kidney to excrete sodium through a tubular independent mechanism contributing to reduce SBP.

scholarly journals Mesenchymal Stem Cells (MSC) Prevented the Progression of Renovascular Hypertension, Improved Renal Function and Architecture

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78464 ◽  
Author(s):  
Elizabeth B. Oliveira-Sales ◽  
Edgar Maquigussa ◽  
Patricia Semedo ◽  
Luciana G. Pereira ◽  
Vanessa M. Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Renovascular Hypertension

scholarly journals 3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13676
Author(s):  
Yuejiao Yang ◽  
Apoorv Kulkarni ◽  
Gian Domenico Soraru ◽  
Joshua M. Pearce ◽  
Antonella Motta
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
3D Printing ◽  
Pore Size ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Low Cost ◽  
Human Mesenchymal Stem Cells ◽  
Bone Tissue Regeneration ◽  
Gene Expressions

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Synovial Mesenchymal Stem Cells Derived From the Cotyloid Fossa Synovium Have Higher Self-renewal and Differentiation Potential Than Those From the Paralabral Synovium in the Hip Joint

2018 ◽  
Vol 46 (12) ◽  
pp. 2942-2953 ◽  
Author(s):  
Yoichi Murata ◽  
Soshi Uchida ◽  
Hajime Utsunomiya ◽  
Akihisa Hatakeyama ◽  
Hirotaka Nakashima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Femoroacetabular Impingement ◽  
Impingement Syndrome ◽  
Cartilage Tissue ◽  
Gene Expressions ◽  
Differentiation Potential ◽  
Femoroacetabular Impingement Syndrome ◽  
And Cartilage

Background: Several studies have shown the relationship between poorer clinical outcomes of arthroscopic femoroacetabular impingement syndrome surgery and focal chondral defects or global chondromalacia/osteoarthritis. Although recent studies described good outcomes after the conjunctive application of synovial mesenchymal stem cells (MSCs), none demonstrated the application of synovial MSCs for cartilaginous hip injuries. Purpose: To compare the characteristics of MSCs derived from the paralabral synovium and the cotyloid fossa synovium and determine which is the better source. Study Design: Controlled laboratory study. Methods: Synovium was harvested from 2 locations of the hip—paralabral and cotyloid fossa—from 18 donors. The number of cells, colony-forming units, viability, and differentiation capacities of adipose, bone, and cartilage were collected and compared between groups. In addition, real-time polymerase chain reaction was used to assess the differentiation capacity of adipose, bone, and cartilage tissue from both samples. Results: The number of colonies and yield obtained at passage 0 of synovium from the cotyloid fossa was significantly higher than that of the paralabral synovium ( P < .01). In adipogenesis experiments, the frequency of detecting oil red O–positive colonies was significantly higher in the cotyloid fossa than in the paralabral synovium ( P < .05). In osteogenesis experiments, the frequency of von Kossa and alkaline phosphatase positive colonies was higher in the cotyloid fossa synovium than in the paralabral synovium ( P < .05). In chondrogenic experiments, the chondrogenic pellet culture and the gene expressions of COL2a1 and SOX9 were higher in the cotyloid fossa synovium than in the paralabral synovium ( P < .05). Conclusion: MSCs from the cotyloid fossa synovium have higher proliferation and differentiation potential than do those from the paralabral synovium and are therefore a better source. Clinical Relevance: Synovial cells from the cotyloid fossa synovium of patients with femoroacetabular impingement syndrome are more robust in vitro, suggesting that MSCs from this source may be strongly considered for stem cell therapy.

scholarly journals Comparison of the Effects of Mesenchymal Stem Cells with Their Extracellular Vesicles on the Treatment of Kidney Damage Induced by Chronic Renal Artery Stenosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Crysthiane Saveriano Rubiao Andre Ishiy ◽  
Milene Subtil Ormanji ◽  
Edgar Maquigussa ◽  
Rosemara Silva Ribeiro ◽  
Antonio da Silva Novaes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Chronic Hypoxia ◽  
Progressive Increase ◽  
Artery Stenosis ◽  
Irreversible Damage ◽  
Whole Cells

Background. Chronic renal artery stenosis is considered one of the most common causes of renovascular hypertension (RH). Chronic hypoxia can lead to irreversible damage to renal tissue and to a progressive deterioration of renal function. We have previously shown that bone marrow-derived mesenchymal stem cells (BMSCs) improved renal parenchyma and function in a model of RH (2 kidneys, 1 clip model (2K-1C) in rats. Microvesicles (MVs) and exosomes (EXs) released by MSCs have been shown to induce effects similar to those induced by whole cells but with fewer side effects. In this study, we compared the effects of adipose-derived MSCs (ASCs) with those of the MVs and EXs released by ASCs on tissue inflammation and renal function in 2 K-1C rats. Results. Flow cytometry analysis showed that even after 15 days, ASCs were still detected in both kidneys. The expression of a stem cell homing marker (SDF1-α) was increased in ASC-treated animals in both the stenotic and contralateral kidneys. Interestingly, SDF1-α expression was also increased in MV- and EX-treated animals. A hypoxia marker (HIF1-α) was upregulated in the stenotic kidney, and treatments with ASCs, MVs, and EXs were effective in reducing the expression of this marker. Stenotic animals showed a progressive increase in systolic blood pressure (SBP), while animals treated with ASCs, MVs, and EXs showed a stabilization of SBP, and this stabilization was similar among the different treatments. Stenotic animals developed significant proteinuria, which was reduced by ASCs and MVs but not by EXs. The increased expression of Col I and TGFβ in both kidneys was reduced by all the treatments, and these treatments also effectively increased the expression of the anti-inflammatory cytokine IL-10 in both kidneys; however, only ASCs were able to reduce the overexpression of the proinflammatory cytokine IL-1β in both kidneys of 2K-1C animals. Conclusion. The results of this study demonstrated that the EVs released by ASCs produced beneficial results but with lower efficacy than whole cells. ASCs produced stronger effects in this model of renal chronic hypoxia, and the use of EVs instead of whole cells should be evaluated depending on the parameter to be corrected.

The Effect of Mesenchymal Stem Cells as a Cell Therapy in Renal Ischemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4756-4756
Author(s):  
Dae Sik Hong ◽  
Seongkyu Park ◽  
Jong-Ho Won ◽  
Chan Kyu Kim ◽  
Sang Chul Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Renal Failure ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Y Chromosome ◽  
Renal Injury ◽  
Female Rats ◽  
Sprague Dawley ◽  
Creatinine Concentration ◽  
Histologic Evaluation

Abstract Introduction: The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Materials and methods: Sprague-Dawley female rats (8 weeks old, 182.2 ± 7.2g) were underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 × 106 cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-hr urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. Results: No significant differences in blood urea nitrogen and creatinine concentration were observed between MSC group and untreated CRF group. However, the weight gain and creatinine clearance in the MSC group were greater than those of the CRF group. Proteinuria in the MSC group was less after 4 months. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. Conclusions: These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.

scholarly journals Effects of mesenchymal stem cells in renovascular hypertension

2015 ◽  
Vol 100 (5) ◽  
pp. 491-495 ◽  
Author(s):  
Elizabeth B. Oliveira-Sales ◽  
Vanessa A. Varela ◽  
Cassia T. Bergamaschi ◽  
Ruy R. Campos ◽  
Mirian A. Boim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renovascular Hypertension

scholarly journals Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells

2017 ◽  
Vol 242 (6) ◽  
pp. 645-656 ◽  
Author(s):  
Baskar Subramani ◽  
Sellamuthu Subbannagounder ◽  
Chithra Ramanathanpullai ◽  
Sekar Palanivel ◽  
Rajesh Ramasamy
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Ascorbic Acid ◽  
Mesenchymal Stem Cells ◽  
Ion Channel ◽  
Oxygen Species ◽  
Gene Expressions ◽  
Redox Imbalance ◽  
Channel Gene ◽  
Ion Channel Gene

Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2 or ascorbic acid at a concentration of 400 µmol/L. Ascorbic acid pre-treated cells remarkably ameliorated the reactive oxygen species level when treated with H2O2. The endogenous antioxidative enzyme gene (Sod1, Sod2, TRXR1 and Gpx1) expressions were escalated in both MSCs in response to reactive oxygen species elevation. In contrast, ascorbic acid pre-treated hUC-MSCs attenuated considerable anti-oxidative gene (TRXR1 and Gpx1) expressions, but not the hC-MSCs. Similarly, the cardiogenic gene (Nkx 2.5, Gata4, Mlc2a and β-MHC) and ion-channel gene ( IKDR, IKCa, Ito and INa.TTX) expressions were significantly increased in both MSCs on the oxidative state. On the contrary, reduced environment could not alter the ion-channel gene expression and negatively regulated the cardiogenic gene expressions except for troponin-1 in both cells. In conclusion, redox imbalance potently alters the cardiac-resident and non-resident MSCs stemness, cardiogenic, and ion-channel gene expressions. In comparison with cardiac-resident MSC, non-resident umbilical cord-MSC has great potential to tolerate the redox imbalance and positively respond to cardiac regeneration. Impact statement Human mesenchymal stem cells (h-MSCs) are highly promising candidates for tissue repair in cardiovascular diseases. However, the retention of cells in the infarcted area has been a major challenge due to its poor viability and/or low survival rate after transplantation. The regenerative potential of mesenchymal stem cells (MSCs) repudiate and enter into premature senescence via oxidative stress. Thus, various strategies have been attempted to improve the MSC survival in ‘toxic’ conditions. Similarly, we investigated the response of cardiac resident MSC (hC-MSCs) and non-resident MSCs against the oxidative stress induced by H2O2. Supplementation of ascorbic acid (AA) into MSCs culture profoundly rescued the stem cells from oxidative stress induced by H2O2. Our data showed that the pre-treatment of AA is able to inhibit the cell death and thus preserving the viability and differentiation potential of MSCs.

scholarly journals Mesenchymal stem cells attenuate renal inflammation, microvascular rarefaction and fibrosis in the renovascular hypertension rat model.

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Mirian A Boim ◽  
Elizabeth B Oliveira‐Sales ◽  
Edgar Maquigussa ◽  
Patricia Semedo ◽  
Luciana G Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renovascular Hypertension ◽  
Rat Model ◽  
Renal Inflammation ◽  
Microvascular Rarefaction

scholarly journals Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Tian Chen ◽  
Yamei Jiang ◽  
Shihao Xu ◽  
Yin Celeste Cheuk ◽  
Jiyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pi3k Pathway ◽  
Poly I:C ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.

scholarly journals Genetic profiling of human bone marrow and adipose tissue-derived mesenchymal stem cells reveals differences in osteogenic signaling mediated by graphene

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Amber F. MacDonald ◽  
Ruby D. Trotter ◽  
Christopher D. Griffin ◽  
Austin J. Bow ◽  
Steven D. Newby ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cellular Adhesion ◽  
Bone Diseases ◽  
Low Oxygen ◽  
Gene Expressions ◽  
Time Point

Abstract Background In the last decade, graphene surfaces have consistently supported osteoblast development of stem cells, holding promise as a therapeutic implant for degenerative bone diseases. However, until now no study has specifically examined the genetic changes when stem cells undergo osteogenic differentiation on graphene. Results In this study, we provide a detailed overview of gene expressions when human mesenchymal stem cells (MSCs) derived from either adipose tissue (AD-MSCs) or bone marrow (BM-MSCs), are cultured on graphene. Genetic expressions were measured using osteogenic RT2 profiler PCR arrays and compared either over time (7 or 21 days) or between each cell source at each time point. Genes were categorized as either transcriptional regulation, osteoblast-related, extracellular matrix, cellular adhesion, BMP and SMAD signaling, growth factors, or angiogenic factors. Results showed that both MSC sources cultured on low oxygen graphene surfaces achieved osteogenesis by 21 days and expressed specific osteoblast markers. However, each MSC source cultured on graphene did have genetically different responses. When compared between each other, we found that genes of BM-MSCs were robustly expressed, and more noticeable after 7 days of culturing, suggesting BM-MSCs initiate osteogenesis at an earlier time point than AD-MSCs on graphene. Additionally, we found upregulated angiogenic markers in both MSCs sources, suggesting graphene could simultaneously attract the ingrowth of blood vessels in vivo. Finally, we identified several novel targets, including distal-less homeobox 5 (DLX5) and phosphate-regulating endopeptidase homolog, X-linked (PHEX). Conclusions Overall, this study shows that graphene genetically supports differentiation of both AD-MSCs and BM-MSCs but may involve different signaling mechanisms to achieve osteogenesis. Data further demonstrates the lack of aberrant signaling due to cell-graphene interaction, strengthening the application of specific form and concentration of graphene nanoparticles in bone tissue engineering. Graphic abstract

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