scholarly journals Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

2021 ◽  
Author(s):  
Ou Zhou ◽  
Jingyi You ◽  
Xiaochuan Xu ◽  
Jiang Liu ◽  
Huijun Qiu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Lung Function ◽  
Umbilical Cord ◽  
Rat Model ◽  
Lung Inflammation ◽  
Human Umbilical Cord ◽  
Alveolar Development ◽  
And Function

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.

Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sushmitha Sriramulu ◽  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Human Keratinocytes ◽  
Human Umbilical Cord ◽  
Hacat Cells ◽  
And Migration

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

scholarly journals hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

2019 ◽  
Vol 28 (12) ◽  
pp. 1552-1559 ◽  
Author(s):  
Jianwei Xu ◽  
Zhanhui Feng ◽  
Xianyao Wang ◽  
Ying Xiong ◽  
Lan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Hypoxic Ischemic Encephalopathy ◽  
Human Umbilical Cord ◽  
Motor Functions ◽  
Ischemic Encephalopathy

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

Human Umbilical Cord Mesenchymal Stem Cells Efficiently Improve Neurobehavioral Status and Alleviate Brain Injury in Hypoxia/Ischemia-Induced Cerebral Palsy Rat Model Via Down-Regulating the Nogoa/Ngr/Rho Pathway

2021 ◽  
Author(s):  
Yaoling Luo ◽  
Zhengyi He ◽  
Minhong Zhang ◽  
Zhengwei Zou ◽  
Lincai Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Mesenchymal Stem Cells ◽  
Cerebral Palsy ◽  
Brain Injury ◽  
Umbilical Cord ◽  
Rat Model ◽  
Human Umbilical Cord ◽  
Hypoxia Ischemia ◽  
Brain Tissues

Abstract Background: Cerebral palsy (CP) is a brain injury disease, which is a global public health issue with an estimated prevalence of 2‰—4‰ and imposes a substantial health burden on many countries. At present, there is no ideal treatment available and most of them will still suffer adverse outcomes. Human umbilical cord mesenchymal stem cells(HUCMSCs) application in many fields of medicine, which can promote nervous system regeneration and inhibit neuroinflammation. The regeneration of central nervous system(CNS) is related to the nervous regeneration inhibitors. NogoA/NgR/Rho pathway is very important to the nerve growth, CP injury is inevitably accompanied by the regeneration and repair of neurons and axons. so we hypothesized that NogoA/NgR/Rho pathway is involved in when using the HUCMSCs to treatment cerebral palsy.Purpose: In this study, we might clarify the NogoA/NgR/Rho pathway functional role in mediating HUCMSCs to improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP rat model.Methods: The CP rat model was established by ligating the left common carotid artery and anoxia for 2.5 h, and HUCMSCs were intravenous injected to the modeled rats. The neurobehavioral situation and brain pathological injury in CP rats were determined via a series of assays. The mRNA and protein expression of NogoA、NgR、RhoA、Rac-1、Cdc42 in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. Results: The CP rats exhibited obvious motor function abnormalities, pathological damage and a lot of brain nerve cell apoptosis. Compared with CP+PBS group and CP group rats, HUCMSCs transplantation can significantly improve the neurobehavioral situation, attenuated brain pathological injury, inhibit apoptosis of brain nerve cells and the activation of astrocytes in CP rats. The expression of NogoA、NgR、RhoA relative mRNA and protein in brain tissues of rats in the CP+PBS group and CP group rats were significantly lower than those of in the sham+PBS and CP+HUCMSCs group. The expression of Rac-1、Cdc42 relative mRNA and protein in brain tissues of rats in the sham and CP+HUCMSCs group was significantly higher than those of in CP+PBS group and CP group rats. Conclusion: This study confirmed that HUCMSCs can efficiently improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced cerebral palsy rat model via down-regulating the NogoA/NgR/Rho pathway.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced Premature Ovarian Failure Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dan Song ◽  
Yun Zhong ◽  
Chunfeng Qian ◽  
Qinyan Zou ◽  
Jian Ou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Hormone Secretion ◽  
Ovarian Failure ◽  
Human Umbilical Cord ◽  
Ovarian Cells

Premature ovarian failure (POF) is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX-) induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL) and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs) in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescencein situhybridization (FISH). The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

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