Lung Epithelial Cells Induce Endodermal Differentiation in Mouse Mesenchymal Bone Marrow Stem Cells by Paracrine Mechanism

Попов, Б. В.; Serikov, Vladimir B.; Петров, Н. С.; Izusova, Tatiana V.; Gupta, Naveen; Matthay, Michael A.

doi:10.1089/ten.2007.0001

Cited by 50 publications

(40 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This in vivo plasticity is further supported by our in vitro co-culture experiments showing that MSCs express SP-C and produce lamellar bodies when exposed to a lung microenvironment. This is consistent with previous in vitro demonstration of embryonic stem cells and MSCs (36)(37)(38)(39)(40) transdifferentiating into AEC2 and suggests that soluble factors play a role in instructing MSCs to adopt the phenotype of the homing organ. One mechanism we did not address for the in vivo plasticity of the MSCs is cellular fusion.…”

Section: Lung Engraftment Transdifferentiation and Paracrine Activisupporting

confidence: 92%

Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

Haaften¹,

Byrne²,

Bonnet³

et al. 2009

Am J Respir Crit Care Med

413

406

View full text Add to dashboard Cite

Rationale: Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown. Objectives: We hypothesized that intratracheal delivery of BMSCs would prevent alveolar destruction in experimental BPD. Methods: In vitro, BMSC differentiation and migration were assessed using co-culture assays and a modified Boyden chamber. In vivo, the therapeutic potential of BMSCs was assessed in a chronic hyperoxiainduced model of BPD in newborn rats. Measurements and Main Results: In vitro, BMSCs developed immunophenotypic and ultrastructural characteristics of type II alveolar epithelial cells (AEC2) (surfactant protein C expression and lamellar bodies) when co-cultured with lung tissue, but not with culture medium alone or liver. Migration assays revealed preferential attraction of BMSCs toward oxygen-damaged lung versus normal lung. In vivo, chronic hyperoxia in newborn rats led to air space enlargement and loss of lung capillaries, and this was associated with a decrease in circulating and resident lung BMSCs. Intratracheal delivery of BMSCs on Postnatal Day 4 improved survival and exercise tolerance while attenuating alveolar and lung vascular injury and pulmonary hypertension. Engrafted BMSCs coexpressed the AEC2-specific marker surfactant protein C. However, engraftment was disproportionately low for cell replacement to account for the therapeutic benefit, suggesting a paracrine-mediated mechanism. In vitro, BMSC-derived conditioned medium prevented O 2 -induced AEC2 apoptosis, accelerated AEC2 wound healing, and enhanced endothelial cord formation. Conclusions: BMSCs prevent arrested alveolar and vascular growth in part through paracrine activity. Stem cell-based therapies may offer new therapeutic avenues for lung diseases that currently lack efficient treatments.

show abstract

Section: Lung Engraftment Transdifferentiation and Paracrine Activisupporting

confidence: 92%

Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

Haaften¹,

Byrne²,

Bonnet³

et al. 2009

Am J Respir Crit Care Med

413

406

View full text Add to dashboard Cite

show abstract

“…For MSC differentiation into epithelial cell lineages, Wnt/ b-catenin signaling also plays a critical role (Popov et al, 2007;Rabbani et al, 2011). GSK-3b could down-regulate the Wnt/ b-catenin signaling by phosphorylation and inactivation of b-catenin (Ling et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells could acquire the phenotypes of epithelial cells and accelerate vaginal reconstruction combined with small intestinal submucosa

Liu

Zhang

et al. 2015

Cell Biology International

View full text Add to dashboard Cite

Grafting material for vaginal reconstruction commonly includes the bowel, peritoneum, skin, and amniotic membrane. Bone marrow mesenchymal stem cells (MSCs) have the potential of multilineage differentiation into a variety of cells and have been widely explored in tissue engineering. In the current study, we examined whether MSCs could be differentiated to vaginal epithelial cells (VECs) upon co-culturing with VECs. We also examined whether Wnt/β-catenin signaling pathway is implicated in such differentiation. Co-culture of MSCs with VECs using a transwell insert system (with no direct contact) induced the expression of VECs marker AE1/AE3 in MSCs. MSCs combined with small intestinal submucosa (SIS) scaffold were implanted in place of the native vagina in rats to observe the implications for vaginal reconstruction in vivo. Anatomic repair of neovagina was assessed by histological staining for H/E and Masson's Trichrome. GSK-3β and β-catenin, main members of Wnt/β-catenin signaling pathway, in MSCs were increased upon co-culturing with VECs. Exposure of co-cultured MSCs to a Wnt/β-catenin signaling activator, lithium chloride (LiCl, 20 µM) increased phosphorylated GSK-3β and β-catenin and enhanced expression of AE1/AE3. In vivo-grafted cells displayed significant matrix infiltration and expressed epithelial markers in neovagina. These findings suggest that MSCs could acquire the phenotype of VECs when co-cultured with VECs, possibly via activation of Wnt/β-catenin signaling. MSCs provide an alternative cell source for potential use in vaginal tissue engineering.

show abstract

“…In addition to staining for CD133, immunofluorescent staining was performed for markers of human embryonic stem cells Oct-4, Nanog, and SSEA-3. Cell differentiation was performed as described (31,32).…”

Section: Primary Cultures Of Placental Stromal Plastic-adherent Cellsmentioning

confidence: 99%

Characterization of an acyl-coenzyme A binding protein predominantly expressed in human primitive progenitor cells

Soupène¹,

Serikov²,

Kuypers³

2008

Journal of Lipid Research

View full text Add to dashboard Cite

Human acyl-coenzyme A binding domain-containing member 6 (ACBD6) is a modular protein that carries an acyl-CoA binding domain at its N terminus and two ankyrin motifs at its C terminus. ACBD6 binds long-chain acyl-CoAs with a strong preference for unsaturated, C18: 1-CoA and C20:4-CoA, over saturated, C16:0-CoA, acyl species. Deletion of the C terminus, which is not conserved among the members of this family, did not affect the binding capacity or the substrate specificity of the protein.

show abstract

Lung Epithelial Cells Induce Endodermal Differentiation in Mouse Mesenchymal Bone Marrow Stem Cells by Paracrine Mechanism

Cited by 50 publications

References 38 publications

Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

Airway Delivery of Mesenchymal Stem Cells Prevents Arrested Alveolar Growth in Neonatal Lung Injury in Rats

Bone marrow mesenchymal stem cells could acquire the phenotypes of epithelial cells and accelerate vaginal reconstruction combined with small intestinal submucosa

Characterization of an acyl-coenzyme A binding protein predominantly expressed in human primitive progenitor cells

Contact Info

Product

Resources

About