scholarly journals Lung Mesenchymal Stem Cells Ameliorate Elastase-Induced Damage in an Animal Model of Emphysema

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Donato Cappetta ◽  
Antonella De Angelis ◽  
Giuseppe Spaziano ◽  
Gioia Tartaglione ◽  
Elena Piegari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Tissue Response ◽  
Airflow Limitation ◽  
Aquaporin 5 ◽  
Intratracheal Administration ◽  
Epithelial Phenotype ◽  
Mean Linear Intercept

Pulmonary emphysema is a respiratory condition characterized by alveolar destruction that leads to airflow limitation and reduced lung function. Although with extensive research, the pathophysiology of emphysema is poorly understood and effective treatments are still missing. Evidence suggests that mesenchymal stem cells (MSCs) possess the ability to engraft the injured tissues and induce repair via a paracrine effect. Thus, the aim of this study was to test the effects of the intratracheal administration of lung-derived mouse MSCs in a model of elastase-induced emphysema. Pulmonary function (static lung compliance) showed an increased stiffness induced by elastase, while morphometric findings (mean linear intercept and tissue/alveolar area) confirmed the severity of alveolar disruption. Contrarily, MSC administration partially restored lung elasticity and alveolar architecture. In the absence of evidence that MSCs acquired epithelial phenotype, we detected an increased proliferative activity of aquaporin 5- and surfactant protein C-positive lung cells, suggesting MSC-driven paracrine mechanisms. The data indicate the mediation of hepatocyte growth factor in amplifying MSC-driven tissue response after injury. Our study shed light on supportive properties of lung-derived MSCs, although the full identification of mechanisms orchestrated by MSCs and responsible for epithelial repair after injury is a critical aspect yet to be achieved.

scholarly journals Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hsiu-Chu Chou ◽  
Chien-Hsiang Chang ◽  
Chien-Han Chen ◽  
Willie Lin ◽  
Chung-Ming Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Injury ◽  
Umbilical Cord ◽  
Daily Administration ◽  
Vascular Density ◽  
Human Umbilical Cord ◽  
Neonatal Rats ◽  
Vegf Expression ◽  
Intratracheal Administration

Abstract Background Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. Methods Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. Results The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Conclusions Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

Pulmonary dysfunction in neonatal SP-B-deficient mice

1997 ◽  
Vol 273 (4) ◽  
pp. L875-L882 ◽  
Author(s):  
Keisuke Tokieda ◽  
Jeffrey A. Whitsett ◽  
Jean C. Clark ◽  
Timothy E. Weaver ◽  
Kazushige Ikeda ◽  
...  
Keyword(s):  
Critical Role ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Phospholipid Content ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Lung Expansion ◽  
B Mice ◽  
Deficient Mice

Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/− mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/− mice, lung volumes and compliances were decreased markedly in homozygous SP-B−/− mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B−/− mice and was reduced in the SP-B+/− mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/− and SP-B−/− mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B−/− mice and in reduced lung compliance in SP-B+/+ and SP-B+/− mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

scholarly journals Magnetic ion channel activation of TREK1 in human mesenchymal stem cells using nanoparticles promotes osteogenesis in surrounding cells

2018 ◽  
Vol 9 ◽  
pp. 204173141880869 ◽  
Author(s):  
James R Henstock ◽  
Michael Rotherham ◽  
Alicia J El Haj
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ion Channel ◽  
Human Mesenchymal Stem Cells ◽  
Host Tissue ◽  
Tissue Response ◽  
Superparamagnetic Nanoparticles ◽  
Surrounding Tissue ◽  
Channel Activation ◽  
Magnetic Ion

Magnetic ion channel activation technology uses superparamagnetic nanoparticles conjugated with targeting antibodies to apply mechanical force directly to stretch-activated ion channels on the cell surface, stimulating mechanotransduction and downstream processes. This technique has been reported to promote differentiation towards musculoskeletal cell types and enhance mineralisation. Previous studies have shown how mesenchymal stem cells injected into a pre-mineralised environment such as a foetal chick epiphysis, results in large-scale osteogenesis at the target site. However, the relative contributions of stem cells and surrounding host tissue has not been resolved, that is, are the mesenchymal stem cells solely responsible for the observed mineralisation or do mechanically stimulated mesenchymal stem cells also promote a host-tissue mineralisation response? To address this, we established a novel two-dimensional co-culture assay, which indicated that magnetic ion channel activation stimulation of human mesenchymal stem cells does not significantly promote migration but does enhance collagen deposition and mineralisation in the surrounding cells. We conclude that one of the important functions of injected human mesenchymal stem cells is to release biological factors (e.g., cytokines and microvesicles) which guide the surrounding tissue response, and that remote control of this signalling process using magnetic ion channel activation technology may be a useful way to both drive and regulate tissue regeneration and healing.

Effect of conditioned medium from mesenchymal stem cells on regeneration of endothelium at HCl-induced damage trachea in rats

2017 ◽  
pp. 28-36
Author(s):  
А.А. Темнов ◽  
А.Г. Волкова ◽  
А.В. Мелерзанов ◽  
В.И. Новоселов
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
De Novo ◽  
Ciliated Cell ◽  
Respiratory Epithelium ◽  
Ciliary Epithelium ◽  
Ciliated Cells ◽  
Intratracheal Administration ◽  
Acid Vapor ◽  
Epithelium Regeneration

Цель - изучение регенерации респираторного эпителия крысы при ингаляционной травме трахеи парами соляной кислоты. Методика. Активация процессов регенерации проводилась после химического ожога путем аппликации в трахею кондиционированной среды, полученной при культивировании аллогенных мезенхимальных стволовых клеток (кМСК). Результаты. Показано, что на 3-и 7-е сут. после аппликации препарата кМСК эпителий трахеи практически полностью восстанавливается. При этом в процессе регенерации в подслизистом слое эпителия образуются замкнутые структуры, содержащие цилиарные клетки, аналогичные реснитчатым клеткам респираторного эпителия трахеи. Эти структуры мигрируют в сторону эпителия и встраиваются в пораженный эпителий. Заключенние. Показано, что препарат кМСК, введенный непосредственно в трахею в ранние сроки после повреждения, способствует восстановлению нормального подслизистого слоя. Было отмечено снижение выраженности воспаления, ускорение темпов миграции цилиарных клеток к поверхности трахеи и формирование реснитчатого эпителия de novo. The purpose. Respiratory epithelium regeneration is studied in rats with tracheal damage induced by inhaling hydrochloric acid vapor. Method. Regeneration process after the chemical burn was activated by intratracheal administration of preparations obtained from the same-species mesenchymal stem cells (MSC). Results. Tracheal epithelium is shown to recover almost completely on day 3-7 after applying MSC compositions (MSCs). Closed structures containing ciliated cells similar to ciliated cells of the respiratory epithelium lining the trachea are formed in the submucosal epithelium during regeneration. These structures migrate towards epithelium and get incorporated into the damaged epithelium. This phenomenon is apparently indicative of the special mechanism of respiratory epithelium regeneration after HCl-induced injury. Conclusion. It is demonstrated in this study that cell-free MSCs instilled intratracheally promote the recovery of normal submucosal epithelium by either preventing or reducing necrosis and inflammation. Such topical MSCs administration significantly accelerates migration of ciliated cell towards the surface and de novo formation of the ciliary epithelium.

scholarly journals Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Annalucia Carbone ◽  
Roberto Zefferino ◽  
Elisa Beccia ◽  
Valeria Casavola ◽  
Stefano Castellani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chloride Channel ◽  
Connexin 43 ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Channel Activity ◽  
Before And After ◽  
Epithelial Phenotype ◽  
Amniotic Mesenchymal Stem Cells

We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

scholarly journals Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

2012 ◽  
Vol 21 (13) ◽  
pp. 2495-2507 ◽  
Author(s):  
Fei Yi ◽  
Muhammad Khan ◽  
Hongwen Gao ◽  
Feng Hao ◽  
Meiyan Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Aquaporin 5 ◽  
Differentiation Capacity

scholarly journals Bone Marrow Aspirate Concentrate for Cartilage Defects of the Knee: From Bench to Bedside Evidence

Cartilage ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Eric J. Cotter ◽  
Kevin C. Wang ◽  
Adam B. Yanke ◽  
Susan Chubinskaya
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Clinical Data ◽  
Bone Marrow Aspirate ◽  
Tissue Response ◽  
Cartilage Defects ◽  
Injection Timing ◽  
Bone Marrow Aspirate Concentrate ◽  
And Cartilage

Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including [“bone marrow aspirate” and “cartilage”], [“mesenchymal stem cells” and “cartilage”], and [“bone marrow aspirate” and “mesenchymal stem cells” and “orthopedics”]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived–mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

Sign in / Sign up

Export Citation Format

Share Document