Transdifferentiation of mesenchymal stem cells derived from human fetal lung to hepatocyte-like cells

SummaryThe bud tip epithelium of the branching mouse and human lung contains multipotent progenitors that are able to self-renew and give rise to all mature lung epithelial cell types. The current study aimed to understand the developmental signaling cues that regulate bud tip progenitor cells in the human fetal lung, which are present during branching morphogenesis, and to use this information to induce a bud tip progenitor-like population from human pluripotent stem cells (hPSCs) in vitro. We identified that FGF7, CHIR-99021 and RA maintained isolated human fetal lung epithelial bud tip progenitor cells in an undifferentiated state in vitro, and led to the induction of a 3-dimensional lung-like epithelium from hPSCs. 3-dimensional hPSC-derived lung tissue was initially patterned, with airway-like interior domains and bud tip-like progenitor domains at the periphery. Epithelial bud tip-like domains could be isolated, expanded and maintained as a nearly homogeneous population by serial passaging. Comparisons between human fetal lung epithelial bud tip cells and hPSC-derived bud tip-like cells were carried out using immunostaining, in situ hybridization and transcriptome-wide analysis, and revealed that in vitro derived tissue was highly similar to native lung. hPSC-derived epithelial bud tip-like structures survived in vitro for over 16 weeks, could be easily frozen and thawed and maintained multi-lineage potential. Furthermore, hPSC-derived epithelial bud tip progenitors successfully engrafted in the proximal airways of injured immunocompromised NSG mouse lungs, where they persisted for up to 6 weeks and gave rise to several lung epithelial lineages.

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Characterization and Neural Differentiation of Fetal Lung Mesenchymal Stem Cells.

Blood ◽

10.1182/blood.v104.11.4177.4177 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4177-4177

Author(s):

Zhong Chao Han ◽

Cun Gang ◽

Feng Wu ◽

Qing Jun ◽

Shi Hong ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Flow Cytometric Analysis ◽

Fetal Lung ◽

Neural Cells ◽

Alternative Source ◽

Differentiation Potential ◽

Cell Based Therapy ◽

Mesenchymal Differentiation ◽

M Phase

Abstract Mesenchymal stem cells (MSCs) have been successfully isolated from a broad range of adult, fetal and other non-embryonic tissues. Fetal lung has been identified as a rich source of MSCs capable of differentiating into multilineage cells of mesenchymal origin. However, the biological characteristics and differentiation potential of fetal lung MSCs remain to be explored. In this study, we have established a series of methods for isolation and expansion of fetal lung MSCs. These MSCs could withstand 40 passages without obvious decline in proliferation ability, significant changes in morphology and expression of cell markers. Cell cycle analysis revealed that when the MSCs reached their log phase of growth, more than 90% of the cells were in G0-G1 phase while the proportion of cells in S phase and G2-M phase were about 5.56% and 2.08% cells individually. Flow cytometric analysis showed that fetal lung MSCs expressed CD13, CD29, CD44, CD90, CD105, D117, CD166 and HLA-ABC, but not CD14, CD31, CD34, CD38, CD41a, CD42b, CD45, CD49d, CD61, CD106, CD133 and HLA-DR. These MSCs could differentiate into neural cells in addition to their mesenchymal differentiation potential. Our data suggest that the fetal lung MSC population is an alternative source of stem cells for cell-based therapy of neurological defects or mesenchymal originated diseases.

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Identification and characterization of pulmonary mesenchymal stem cells derived from rat fetal lung tissue

Tissue and Cell ◽

10.1016/j.tice.2021.101628 ◽

2021 ◽

pp. 101628

Author(s):

Caiyun Ma ◽

Yang Liu ◽

Yingchun Ma ◽

Lijie Jiang ◽

Qianyi Huang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Tissue ◽

Fetal Lung ◽

Identification And Characterization

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Characterization and Neural Differentiation of Fetal Lung Mesenchymal Stem Cells

Cell Transplantation ◽

10.3727/000000005783983070 ◽

2005 ◽

Vol 14 (5) ◽

pp. 311-321 ◽

Cited By ~ 63

Author(s):

Cun Gang Fan ◽

Feng Wu Tang ◽

Qing Jun Zhang ◽

Shi Hong Lu ◽

Hai Ying Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Flow Cytometric Analysis ◽

Fetal Lung ◽

Neural Cells ◽

Alternative Source ◽

Differentiation Potential ◽

Cell Based Therapy ◽

Mesenchymal Differentiation ◽

M Phase

Mesenchymal stem cells (MSCs) have been successfully isolated from a broad range of adult, fetal, and other nonembryonic tissues. Fetal lung has been identified as a rich source of MSCs. However, the biological characteristics and differentiation potential of fetal lung MSCs remain to be explored. In this study, we established a series of methods for isolation and expansion of fetal lung MSCs. These MSCs could withstand more than 40 passages without obvious decline in proliferation ability, significant changes in morphology, and expression of cell markers. Flow cytometric analysis showed that fetal lung MSCs expressed CD13, CD29, CD44, CD90, CD105, CD166, and HLA-ABC, but not CD14, CD31, CD34, CD38, CD41a, CD42b, CD45, CD49d, CD61, CD106, CD133, and HLA-DR. Cell cycle analysis revealed that when the MSCs reached their log phase of growth, more than 90% of the cells were in G0/G1 phase while the proportion of cells in S phase and G2/M phase were about 5.56% and 2.08% cells, respectively. These MSCs could differentiate into neural cells in addition to their mesenchymal differentiation potential. Our data suggest that the fetal lung MSC population is an alternative source of stem cells for cell-based therapy of neurological defects or mesenchymal-originating diseases.

Download Full-text