scholarly journals Umbilical cord mesenchymal stem cells protect thymus structure and function in aged C57 mice by downregulating aging-related genes and upregulating autophagy- and anti-oxidative stress-related genes

Aging ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 16899-16920
Author(s):  
Xing-Hua Pan ◽  
Qing-Keng Lin ◽  
Xiang Yao ◽  
Zi-An Li ◽  
Xue-Min Cai ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Dian Li ◽  
Dan Zhang ◽  
Bo Tang ◽  
Yue Zhou ◽  
Wenhao Guo ◽  
...  

Objective. To investigate whether exosomes from human umbilical cord mesenchymal stem cells (hUC-MSCs) can protect against the toxic effects of oxalate and calcium oxalate monohydrate (COM) crystals in human proximal tubular epithelial (HK-2) cells. Methods. Exosomes were isolated from hUC-MSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the presence of specific biomarkers. HK-2 cells received 1 of 4 treatments: control (cells alone), hUC-MSC exosomes, oxalate+COM, or oxalate+COM and hUC-MSC exosomes. Cell viability was determined using the MTT assay. Oxidative stress was determined by measuring LDH activity and the levels of H2O2, malondialdehyde (MDA), and reactive oxygen species (ROS). Expressions of N-cadherin, TGF-β, and ZO-1 were determined by immunofluorescence. Expressions of epithelial markers, mesenchymal markers, and related signaling pathway proteins were determined by western blotting. Results. After 48 h, cells in the oxalate+COM group lost their adhesion, appeared long, spindle-shaped, and scattered, and the number of cells had significantly decreased. The oxalate+COM treatment also upregulated TGF-β and mesenchymal markers, downregulated epithelial markers, increased the levels of LDH, H2O2, MDA, and ROS, decreased cell viability, and increased cell migration. The isolated exosomes had double-layer membranes, had hollow, circular, or elliptical shapes, had diameters mostly between 30 and 100 nm, and expressed CD9, CD63, and Alix. Treatment of HK-2 cells with hUC-MSC exosomes reversed or partly reversed all the effects of oxalate+COM. Conclusions. Exosomes from hUC-MSCs alleviate the oxidative injury and the epithelial-mesenchymal transformation of HK-2 cells that is induced by oxalate+COM.


2014 ◽  
Vol 11 (3) ◽  
pp. 275-284 ◽  
Author(s):  
Guangyang Liu ◽  
Lihua Wang ◽  
Tianxiang Pang ◽  
Delin Zhu ◽  
Yi Xu ◽  
...  

2016 ◽  
Vol 96 (3) ◽  
pp. 1127-1168 ◽  
Author(s):  
Samuel Golpanian ◽  
Ariel Wolf ◽  
Konstantinos E. Hatzistergos ◽  
Joshua M. Hare

Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Marta Barba ◽  
Claudia Cicione ◽  
Camilla Bernardini ◽  
Fabrizio Michetti ◽  
Wanda Lattanzi

Adipose tissue represents a hot topic in regenerative medicine because of the tissue source abundance, the relatively easy retrieval, and the inherent biological properties of mesenchymal stem cells residing in its stroma. Adipose-derived mesenchymal stem cells (ASCs) are indeed multipotent somatic stem cells exhibiting growth kinetics and plasticity, proved to induce efficient tissue regeneration in several biomedical applications. A defined consensus for their isolation, classification, and characterization has been very recently achieved. In particular, bone tissue reconstruction and regeneration based on ASCs has emerged as a promising approach to restore structure and function of bone compromised by injury or disease. ASCs have been used in combination with osteoinductive biomaterial and/or osteogenic molecules, in either static or dynamic culture systems, to improve bone regeneration in several animal models. To date, few clinical trials on ASC-based bone reconstruction have been concluded and proved effective. The aim of this review is to dissect the state of the art on ASC use in bone regenerative applications in the attempt to provide a comprehensive coverage of the topics, from the basic laboratory to recent clinical applications.


2021 ◽  
Author(s):  
Ou Zhou ◽  
Jingyi You ◽  
Xiaochuan Xu ◽  
Jiang Liu ◽  
Huijun Qiu ◽  
...  

Abstract BackgroundAlthough it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide (LPS)-induced BPD rat model and to clarify the underlying mechanism.MethodsPregnant rats received intra-amniotic injections of LPS on day 20.5 of gestation (term=day 22.5 of gestion), and pups were delivered by cesarean section on embryonic day 22.5 (E22.5). MVs were isolated by ultracentrifugation and then were characterized. hUCMSCs and MVs were administered intratracheally on postnatal day 7 (PN7). On PN14, lung function was measured, and tissues were harvested to determine alveolarization. Immunofluorescence staining was used to determine the co-localization of MVs and lung cells. Cell proliferation was measured by Ki-67 staining, and apoptosis was determined by flow cytometry using 7-ADD and Annexin V. The expression levels of AKT, p38, JNK, ERK, and their phosphorylated forms, PTEN and VEGF, were measured by WB.ResultsAntenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature. Both hUCMSCs and MVs successfully promoted alveolar development and improved lung function. However, hUCMSCs but not MVs restored the loss of pulmonary microvascular vessels (<100 μm). Furthermore, MVs were mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, upregulated expression of p-AKT, downregulated expression of PTEN, as well as inhibition of MAPK pathway were observed in MVs-treated BPD rats.ConclusionsMVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuate lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.


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