scholarly journals Preconditioning of Hypoxic Culture Increases The Therapeutic Potential of Adipose Derived Mesenchymal Stem Cells

2021 ◽  
Vol 9 (F) ◽  
pp. 505-515
Author(s):  
Tito Sumarwoto ◽  
Heri Suroto ◽  
Ferdiansyah Mahyudin ◽  
Dwikora Novembri Utomo ◽  
Romaniyanto Romaniyanto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Chemokine Receptor ◽  
Therapeutic Potential ◽  
Trophic Factors ◽  
Receptor Type ◽  
Angiogenic Growth Factors ◽  
Hypoxic Precondition

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.  

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
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Trophic Factors ◽  
Surface Molecules ◽  
Hla Dr ◽  
Wide Range ◽  
Pleiotropic Properties

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.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

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.

scholarly journals Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells

2021 ◽  
Vol 32 (3) ◽  
Author(s):  
Fatemeh Hejazi ◽  
Vahid Ebrahimi ◽  
Mehrdad Asgary ◽  
Abbas Piryaei ◽  
Mohammad Javad Fridoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Healing ◽  
Critical Size ◽  
Therapeutic Potential ◽  
Rna Extraction ◽  
Osteotomy Site ◽  
Cell Groups ◽  
The Right

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.

Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells (Admscs) and/or Taurine in Aluminum Chloride-Induced Alzheimer's Disease Rat Model

2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Brain Homogenate ◽  
Oxidative Stress Marker

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.

scholarly journals Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells’ engraftment in wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Guo ◽  
Juan Du ◽  
Dan-feng Yuan ◽  
Ya Zhang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Optimal Protocol ◽  
Marrow Mesenchymal Stem Cells ◽  
Gsk 3Β ◽  
Migration Capacity

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.

scholarly journals Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway

2021 ◽  
Vol 22 (21) ◽  
pp. 11356
Author(s):  
Jiaqiang Deng ◽  
Ping Ouyang ◽  
Weiyao Li ◽  
Lijun Zhong ◽  
Congwei Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mrna Expression ◽  
Light Chain ◽  
Therapeutic Potential ◽  
Cell Model ◽  
Biological Aging ◽  
Aging Effects

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

scholarly journals Mesenchymal Stem Cells—Potential Applications in Kidney Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 2462 ◽  
Author(s):  
Benjamin Bochon ◽  
Magdalena Kozubska ◽  
Grzegorz Surygała ◽  
Agnieszka Witkowska ◽  
Roman Kuźniewicz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Clinical Effects ◽  
Potential Applications ◽  
The Subject ◽  
Subcutaneous Adipose

Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.

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