scholarly journals Human Umbilical Cord-Derived Mesenchymal Stem Cells Improve Learning and Memory Function in Hypoxic-Ischemic Brain-Damaged Rats via an IL-8-Mediated Secretion Mechanism Rather than Differentiation Pattern Induction

2015 ◽  
Vol 35 (6) ◽  
pp. 2383-2401 ◽  
Author(s):  
Xiaoqin Zhou ◽  
Jialu Gu ◽  
Yan Gu ◽  
Mulan He ◽  
Yang Bi ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Umbilical Cord ◽  
Memory Function ◽  
Morphological Characteristics ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Ischemic Brain ◽  
Differentiation Pattern

Background: MSCs are a promising therapeutic resource. Paracrine effects and the induction of differentiation patterns are thought to represent the two primary mechanisms underlying the therapeutic effects of mesenchymal stem cell (MSC) transplantation in vivo. However, it is unclear which mechanism is involved in the therapeutic effects of human umbilical cord-derived MSC (hUC-MSC) transplantation. Methods and Results: Based on flow cytometry analysis, hUC-MSCs exhibited the morphological characteristics and surface markers of MSCs. Following directed neural induction, these cells displayed a neuron-like morphology and expressed high levels of neural markers. All types of hUC-MSCs, including differentiated and redifferentiated cells, promoted learning and memory function recovery in hypoxic-ischemic brain damaged (HIBD) rats. The hUC-MSCs secreted IL-8, which enhanced angiogenesis in the hippocampus via the JNK pathway. However, the differentiated and redifferentiated cells did not exert significantly greater therapeutic effects than the undifferentiated hUC-MSCs. Conclusion: hUC-MSCs display the biological properties and neural differentiation potential of MSCs and provide therapeutic advantages by secreting IL-8, which participates in angiogenesis in the rat HIBD model. These data suggest that hUC-MSC transplantation improves the recovery of neuronal function via an IL-8-mediated secretion mechanism, whereas differentiation pattern induction was limited.

scholarly journals In VitroDifferentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Peter Szaraz ◽  
Matthew Librach ◽  
Leila Maghen ◽  
Farwah Iqbal ◽  
Tanya A. Barretto ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Cardiac Regeneration ◽  
First Trimester ◽  
Human Umbilical Cord ◽  
Perivascular Cells ◽  
Differentiation Potential ◽  
Mortality And Morbidity ◽  
Cardiomyogenic Differentiation

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting thatin vitropredifferentiation could be a potential strategy to increase their effectivenessin vivo.

scholarly journals Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

2021 ◽  
Author(s):  
Jianye Wang ◽  
Liu Dong ◽  
Xuan Xu ◽  
Xiaohua Jiang ◽  
Ziwei Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Caspase 3 ◽  
Endometrial Thickness ◽  
Saline Group ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Paracrine Factors

Abstract BackgroundEndometrial injury contributes to impaired endometrial receptivity, and is well recognized as a critical factor in implantation failure. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSCs) mainly depend on their capacity to secrete paracrine factors and are mediated by MSC-derived exosomes (MSC-Exos). In this study, we aimed to explore the effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on injured endometrium in the mouse endometrial damage model and the potential mechanisms for these effects.MethodsAll female mice were randomly divided into control group, saline group, and exosome group. To observe the distribution of exosomes in vivo, DiR-labeled hUCMSC-Exos were injected into the tail vein of endometrium-injured mice. HE staining was used to detect changes in endometrial thickness and number of glands. TUNEL staining was used to detect cells apoptosis. The expression of Ki67 and CD31 was examined by immunohistochemistry. Then, western blotting was used to measure the expression of Bcl-2, Bax, Cleaved Caspase-3, PTEN, AKT and p-AKT. The expression of VEGF and IGF-1 was detected by RT-PCR.ResultshUCMSC-Exos was able to migrate to the damaged endometrium. After hUCMSC-Exos injection, the endometrial thickness and the number of glands were significantly increased (P< 0.05). Compared with the saline group, apoptosis was significantly reduced in the exosome group, and the expression of Ki67 and CD31 was significantly increased (P< 0.05). Besides, the expression of Bax, Cleaved Caspase-3 and PTEN was reduced as hUCMSC-Exos addition, and the Bcl-2 and p-Akt expression was increased. The expression of VEGF and IGF-1 was significantly upregulated in the exosome group compared to the saline group (P< 0.05).ConclusionshUCMSC-Exos ameliorated the damaged uterus, increased endometrial thickness, suppressed apoptosis and improved the cell proliferation in the mouse injured endometrium model. Furthermore, we discovered that hUCMSC-Exos could activate the PTEN/AKT signaling pathways and induce the overexpression of VEGF and IGF-1 in vivo.

scholarly journals Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into HepatocytesIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Gai Xue ◽  
Xiaolei Han ◽  
Xin Ma ◽  
Honghai Wu ◽  
Yabin Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Liver Tissue ◽  
Human Umbilical Cord ◽  
Hepatic Differentiation ◽  
Differentiation Potential ◽  
Tissue Microenvironment

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCsin vitroandin vivoand to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironmentin vivousing liver homogenate supernatant (LHS)in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cellsin vivoin the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes bothin vitroandin vivo.

scholarly journals Isolation and evaluation of biological properties and differentiation potential of human umbilical cord-derived mesenchymal stem cells in covid-19 positive patients

2021 ◽  
Vol 7 (3D) ◽  
pp. 542-551
Author(s):  
Shadi Babaei ◽  
Maryam Mirzaei ◽  
Narges Maleki ◽  
Zahra Alizadeh ◽  
Fahimeh Yasari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Absorption Spectroscopy ◽  
Morphological Characteristics ◽  
Biological Properties ◽  
Human Umbilical Cord ◽  
Differentiation Potential ◽  
Experimental Laboratory ◽  
Physical Examinations

The present study investigated the biological properties of umbilical cord-derived mesenchymal stem cells and their ability to differentiate in patients who have had positive COVID-19 PCR test result during their pregnancies. In this experimental laboratory study, the whole placenta specimens were obtained from 30 positive COVID-19 women undergoing cesarean section, with age 20 to 40 years, and kept under standardized conditions. The mesenchymal cells were isolated by enzymatic method and their morphological characteristics were examined by microscopy and absorption spectroscopy and their biological properties, in particular expression of CD markers, were determined by flow cytometry. Finally, mesenchymal stem cells were cultured in specific media in order to differentiate into osteocyte and adipocyte. Data were analyzed using descriptive statistics. Morphological and physical examinations by microscope and absorption spectroscopy as well as presenting of CD44, CD73, CD90, and CD105 markers and lacking CD34 and CD45 markers demonstrated the mesenchymal entity of stem cells. Mesenchymal stem cells successfully differentiated into osteocyte and adipocyte.

scholarly journals Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongli Li ◽  
Junxiu Zhang ◽  
Zijia Liu ◽  
Yuanyuan Gong ◽  
Zhi Zheng
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Mechanism Of Action ◽  
Epithelial Mesenchymal Transition ◽  
Human Umbilical Cord ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

scholarly journals Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Stimulated by Hypoxia Promote Angiogenesis Both In Vitro and In Vivo

2012 ◽  
Vol 21 (18) ◽  
pp. 3289-3297 ◽  
Author(s):  
Hong-Chao Zhang ◽  
Xin-Bin Liu ◽  
Shu Huang ◽  
Xiao-Yun Bi ◽  
Heng-Xiang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord

scholarly journals Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

2015 ◽  
Vol 35 (9) ◽  
pp. 1435-1444 ◽  
Author(s):  
Tingting Dong ◽  
Qi Zhang ◽  
Michael R Hamblin ◽  
Mei X Wu
Keyword(s):  
Learning And Memory ◽  
Memory Function ◽  
Light Illumination ◽  
Low Level ◽  
Metabolic Substrates ◽  
Secondary Damage ◽  
Injured Brain ◽  
Combinational Treatment

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue–like injured brain.

Effects of Gossypium herbaceam Extract Administration on the Learning and Memory Function in the Naturally Aged Rats: Neuronal Niche Improvement1

2012 ◽  
Vol 31 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Yanyong Liu ◽  
Haji Akber Aisa ◽  
Chao Ji ◽  
Nan Yang ◽  
Haibo Zhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Learning And Memory ◽  
Memory Impairment ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Aged Rats

Aging-associated cognitive impairment is an important health care issue since individuals with mild cognitive impairment are more likely to develop Alzheimer’s disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment associated with aging were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70, and 140 mg/kg exerted an improved effect on the learning and memory impairment in aged rats. Subsequently, GHE afforded a beneficial action on eradication of free radicals without influence on the activity of glutathione peroxidase and superoxide dismutase. GHE treatment enhanced the expression levels of nerve growth factor. Meanwhile, proliferation of neural progenitor cells was elevated in hippocampus after treatment with GHE. Taken together, neurogenic niche improvement could be involved in the mechanism underlying neuroprotection of GHE against aging-associated cognitive impairment. These findings suggested that GHE might be a potential agent as cognitive-enhancing drugs that delay or halt mild cognitive impairment progression to Alzheimer’s disease or treatment of aging-associated cognitive impairment.

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