scholarly journals Mesenchymal Stem Cells as Therapeutic Candidates for Halting the Progression of Diabetic Nephropathy

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Janaina Paulini ◽  
Eliza Higuti ◽  
Rosana M. C. Bastos ◽  
Samirah A. Gomes ◽  
Érika B. Rangel

Mesenchymal stem cells (MSCs) possess pleiotropic properties that include immunomodulation, inhibition of apoptosis, fibrosis and oxidative stress, secretion of trophic factors, and enhancement of angiogenesis. These properties provide a broad spectrum for their potential in a wide range of injuries and diseases, including diabetic nephropathy (DN). MSCs are characterized by adherence to plastic, expression of the surface molecules CD73, CD90, and CD105 in the absence of CD34, CD45, HLA-DR, and CD14 or CD11b and CD79a or CD19 surface molecules, and multidifferentiation capacity in vitro. MSCs can be derived from many tissue sources, consistent with their broad, possibly ubiquitous distribution. This article reviews the existing literature and knowledge of MSC therapy in DN, as well as the most appropriate rodent models to verify the therapeutic potential of MSCs in DN setting. Some preclinical relevant studies are highlighted and new perspectives of combined therapies for decreasing DN progression are discussed. Hence, improved comprehension and interpretation of experimental data will accelerate the progress towards clinical trials that should assess the feasibility and safety of this therapeutic approach in humans. Therefore, MSC-based therapies may bring substantial benefit for patients suffering from DN.

Author(s):  
Dana Foudah ◽  
Juliana Redondo ◽  
Cristina Caldara ◽  
Fabrizio Carini ◽  
Giovanni Tredici ◽  
...  

AbstractMesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into mesodermal lineages (osteogenic, adipogenic, chondrogenic), but also towards non-mesodermal derivatives (e.g. neural cells). Recent in vitro studies revealed that, in the absence of any kind of differentiation stimuli, undifferentiated MSCs express neural differentiation markers, but the literature data do not all concur. Considering their promising therapeutic potential for neurodegenerative diseases, it is very important to expand our knowledge about this particular biological property of MSCs. In this study, we confirmed the spontaneous expression of neural markers (neuronal, glial and progenitor markers) by undifferentiated human MSCs (hMSCs) and in particular, we demonstrated that the neuronal markers βIII-tubulin and NeuN are expressed by a very high percentage of hMSCs, regardless of the number of culture passages and the culture conditions. Moreover, the neuronal markers βIII-tubulin and NeuN are still expressed by hMSCs after in vitro osteogenic and adipogenic differentiation. On the other hand, chondrogenically differentiated hMSCs are negative for these markers. Our findings suggest that the expression of neuronal markers could be common to a wide range of cellular types and not exclusive for neuronal lineages. Therefore, the expression of neuronal markers alone is not sufficient to demonstrate the differentiation of MSCs towards the neuronal phenotype. Functional properties analysis is also required.


2021 ◽  
Vol 9 (F) ◽  
pp. 505-515
Author(s):  
Tito Sumarwoto ◽  
Heri Suroto ◽  
Ferdiansyah Mahyudin ◽  
Dwikora Novembri Utomo ◽  
Romaniyanto Romaniyanto ◽  
...  

Various in vitro preconditioning strategies have been implemented to increase the regenerative capacity of MSCs. Among them are modulation of culture atmosphere (hypoxia or anoxia), three-dimensional culture (3D), addition of trophic factors (in the form of growth factors, cytokines or hormones), lipopolysaccharides, and pharmacological agents. Preconditioning mesenchymal stem cells by culturing them in a hypoxic environment, which resembles the natural oxygen environment of the tissues (1% –7%) and not with standard culture conditions (21%), increases the survival of these cells via Hypoxia Inducible Factor-1α (HIF-1a) and via Akt-dependent mechanisms. In addition, the hypoxic precondition stimulates the secretion of pro-angiogenic growth factors, increases the expression of chemokines SDF-1 (stromal cell-derived factor-1) and its receptor CXCR4 (chemokine receptor type 4) - CXCR7 (chemokine receptor type 7) and increases engraftment of stem cell. This review aims to provide an overview of the preconditioned hypoxic treatment to increase the therapeutic potential of adipose-derived mesenchymal stem cells.  


2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Gianluca Vadalà ◽  
Luca Ambrosio ◽  
Fabrizio Russo ◽  
Rocco Papalia ◽  
Vincenzo Denaro

Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several in vitro and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.


2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.


Author(s):  
Fatemeh Hejazi ◽  
Vahid Ebrahimi ◽  
Mehrdad Asgary ◽  
Abbas Piryaei ◽  
Mohammad Javad Fridoni ◽  
...  

AbstractOsteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.


2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Guo ◽  
Juan Du ◽  
Dan-feng Yuan ◽  
Ya Zhang ◽  
Shu Zhang ◽  
...  

Abstract Background The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. Objective To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. Methods Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. Results Treatment BMSCs with 50 μM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3β. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. Conclusions The findings suggested that 50 μM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.


2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
K. Marycz ◽  
J. M. Irwin Houston ◽  
C. Weiss ◽  
M. Röcken ◽  
K. Kornicka

Recently, metabolic syndrome (MS) has gained attention in human and animal metabolic medicine. Insulin resistance, inflammation, hyperleptinemia, and hyperinsulinemia are critical to its definition. MS is a complex cluster of metabolic risk factors that together exert a wide range of effects on multiple organs, tissues, and cells in the body. Adipose stem cells (ASCs) are multipotent stem cell population residing within the adipose tissue that is inflamed during MS. Studies have indicated that these cells lose their stemness and multipotency during MS, which strongly reduces their therapeutic potential. They suffer from oxidative stress, apoptosis, and mitochondrial deterioration. Thus, the aim of this study was to rejuvenate these cells in vitro in order to improve their chondrogenic differentiation effectiveness. Pharmacotherapy of ASCs was based on resveratrol and 5-azacytidine pretreatment. We evaluated whether those substances are able to reverse aged phenotype of metabolic syndrome-derived ASCs and improve their chondrogenic differentiation at its early stage using immunofluorescence, transmission and scanning electron microscopy, real-time PCR, and flow cytometry. Obtained results indicated that 5-azacytidine and resveratrol modulated mitochondrial dynamics, autophagy, and ER stress, leading to the enhancement of chondrogenesis in metabolically impaired ASCs. Therefore, pretreatment of these cells with 5-azacytidine and resveratrol may become a necessary intervention before clinical application of these cells in order to strengthen their multipotency and therapeutic potential.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
John Michel ◽  
Matthew Penna ◽  
Juan Kochen ◽  
Herman Cheung

Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs forin vitroandin vivoexperiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.


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