Contributions
Abstract: S138
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00
Location: Room N104
Background
The tunneling nanotube (TNT) is a newly discovered,long and thin tubular structure between cells and can facilitate the intercellular exchange of diverse cellular signals and components ranging from electrical signalling to organelles .
Aims
To investigate the novel intercellular communication TNT between BMMSC and BMdECs or HUVEC, illuminating its constituent and investigating the significance of transport of mitochondrial through TNT between BMMSC and BMdECs or HUVEC suffering from chemotherapy stress of cytosine arabinoside .
Methods
We established two direct co-culture system for human primary bone marrow mesenchymal stem cells(BMMSCs) and bone marrow-derived endothelial cells (BMdECs) or Human umbilical cord vein endothelial cells(HUVECs）respectively.
Results
Firstly, We observed the TNTs formed between BMMSCs and endothelial cells including HUVECs and BMdECs. We identified the TNT structure between BMMSCs and HUVECs or BMdECs are composed with F-actin，microtubule in addition to membrane. Live cell imaging showed the two xenogeneic cells form TNTs by retaining a thin thread of membrane upon dislodgement .Besides,we observed that TNT was more likely to occur between healthy bone marrow mesenchymal stem cell and endothelial cells after cytarabine (Ara-C) treatment. Single-cell analysis showed that stressed endothelial cells and cell lines in the early stages of apoptosis caused by cytarabine (Ara-C) treatment form TNT to interact with untreated BMMSCs and then mesenchymal stem cells transport mitochondria to injured endothelial cell or cell line.Notably,the rescue effect was inhibited when the formation of TNTs were impaired by incubating with an F-actin-depolymerizing drug and tubline -depolymerizing drug, indicated that these TNTs transferring mitochondria have a distinct cytoskeletal composition which composed with F-actin and microtubule. Our results also suggest that the delivery of functional mitochondria from untreated BMMNCs to HUVECs via TNTs can mediate the recovery of injured HUVECs from the apoptosis, contribute to proliferation and remodel the formation of capillary-like structures in Matrigel®-coated plates of HUVECs suffer from chemotherapy stress of Ara-C.
Conclusion
BMMSCs can transfer mitochondria via TNTs formed between endothelial cells and rescued endothelial cells suffering chemotherapy stress,which can alleviate apoptosis of stressed endothelial cells, relieve its proliferation inhibition and alter its formation of capillary-like structures.Our study offers the clues to help know about cell-cell communication of niche components in the HSC niche in bone marrow.
Session topic: 23. Hematopoiesis, stem cells and microenvironment
Keyword(s): Proliferation, Mesenchymal stem cell, Endothelial cell, Apoptosis
Abstract: S138
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 11:45 - 12:00
Location: Room N104
Background
The tunneling nanotube (TNT) is a newly discovered,long and thin tubular structure between cells and can facilitate the intercellular exchange of diverse cellular signals and components ranging from electrical signalling to organelles .
Aims
To investigate the novel intercellular communication TNT between BMMSC and BMdECs or HUVEC, illuminating its constituent and investigating the significance of transport of mitochondrial through TNT between BMMSC and BMdECs or HUVEC suffering from chemotherapy stress of cytosine arabinoside .
Methods
We established two direct co-culture system for human primary bone marrow mesenchymal stem cells(BMMSCs) and bone marrow-derived endothelial cells (BMdECs) or Human umbilical cord vein endothelial cells(HUVECs）respectively.
Results
Firstly, We observed the TNTs formed between BMMSCs and endothelial cells including HUVECs and BMdECs. We identified the TNT structure between BMMSCs and HUVECs or BMdECs are composed with F-actin，microtubule in addition to membrane. Live cell imaging showed the two xenogeneic cells form TNTs by retaining a thin thread of membrane upon dislodgement .Besides,we observed that TNT was more likely to occur between healthy bone marrow mesenchymal stem cell and endothelial cells after cytarabine (Ara-C) treatment. Single-cell analysis showed that stressed endothelial cells and cell lines in the early stages of apoptosis caused by cytarabine (Ara-C) treatment form TNT to interact with untreated BMMSCs and then mesenchymal stem cells transport mitochondria to injured endothelial cell or cell line.Notably,the rescue effect was inhibited when the formation of TNTs were impaired by incubating with an F-actin-depolymerizing drug and tubline -depolymerizing drug, indicated that these TNTs transferring mitochondria have a distinct cytoskeletal composition which composed with F-actin and microtubule. Our results also suggest that the delivery of functional mitochondria from untreated BMMNCs to HUVECs via TNTs can mediate the recovery of injured HUVECs from the apoptosis, contribute to proliferation and remodel the formation of capillary-like structures in Matrigel®-coated plates of HUVECs suffer from chemotherapy stress of Ara-C.
Conclusion
BMMSCs can transfer mitochondria via TNTs formed between endothelial cells and rescued endothelial cells suffering chemotherapy stress,which can alleviate apoptosis of stressed endothelial cells, relieve its proliferation inhibition and alter its formation of capillary-like structures.Our study offers the clues to help know about cell-cell communication of niche components in the HSC niche in bone marrow.
Session topic: 23. Hematopoiesis, stem cells and microenvironment
Keyword(s): Proliferation, Mesenchymal stem cell, Endothelial cell, Apoptosis