Biology subjects

Kang, Y. C.

Publications and source records attributed to Kang, Y. C..

4 recordsLinked to original sources

bioRxiv2024

Human umbilical mesenchymal stem cell-derived mitochondria ameliorate maternal phenotype by improving placental mitochondria and vascular function in angiotensin II-induced preeclampsia rat

BackgroundMitochondrial transplantation (Mito-T) is a novel therapeutic strategy targeting ischemic cardiovascular diseases. Here, we tested the efficacy of human umbilical mesenchymal stem cell-derived mitochondria transplantation (Mito-T) on a rat model of PE. MethodsPE was induced by infusing angiotensin II (Ang II) to SD pregnancy rats on gestation day 8 (GD 8). Mito-T (100 g/l) was injected via jugular vein on GD 14. FindingsOn GD 20, PE rats showed high blood pressure, kidney and placental vascular abnormalities, reduced placental and fetal weights. Injected Mito-T was distributed intensively in the kidney, uterus and placenta of PE rats. Importantly, Mito-T reversed clinical manifestations of PE, restored placental abnormalities and reduced serum sFLT-1 levels and sFLT-1/PlGF ratio. In the placental mitochondria, Mito-T increased ETC complexes (complex I-V), improved mitochondrial membrane potential, ATP synthase and citrate synthase activities and biogenesis markers (PGC-1, TFAM, NRF1) and reduced ROS production. Mito-T increased mitochondrial fusion proteins (OPA1, MFN1 and MFN2), reduced mitochondrial fission proteins (DRP1 and FIS1) and mitophagy proteins (PINK, BNIP3, BNIP3L, FUNDC1), restored sFLT-1 regulating calcineurin-NFAT-dependent pathways in the placental tissue, primary trophoblast cells and Bewo cell line. Furthermore, eNOS, nNOS and AT2R mRNA and protein expressions were restored in placenta and trophoblast cells after Mito-T. InterpretationThis is the first study of PE treatment with Mito-T. Mito-T reverses pathological phenotypes of PE rats by improving placental mitochondrial and vascular function. The results provide proofs of concept of Mito-T as a potential therapeutic strategy for reducing maternal and fetal risks in PE patients. FundingThis work is supported by Korean National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2019R1A2C1005720, NRF-2023R1A2C1005720), BK21 FOUR education program, Korean Society of Hypertension (Grant number KSH-R-2020), National Natural Science Foundation of China (NSFC 31660284, NSFC31860288).

pathology↗

bioRxiv2021

Mesoderm-Derived PDGFRA+ Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta

Mouse hematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5) on the ventral surface of the dorsal aorta, by endothelial-to-hematopoietic transition (EHT). We investigated whether cells with mesenchymal stem cell-like activity, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta- gonad-mesonephros (AGM) and contribute to the structural development of the dorsal aorta and EHT. Using transgenic mice, we demonstrate a lineage hierarchy for AGM stromal cells and traced the E10.5/E11.5 aortic endothelium and HSCs to mesoderm derived (Mesp1) PDGFRA+ stromal cells (Mesp1der PSCs). Mesp1der PSCs dominate the sub-endothelial and ventral stroma in the E10.5-E11.5 AGM but by E13.5 were replaced by neural crest (Wnt1) derived PDGFRA+ stromal cells (Wnt1der PSCs). Co-aggregating non-hemogenic embryonic and adult endothelial cells with Mesp1der PSCs but not with Wnt1der PSCs resulted in activation of a hematopoietic transcriptional program in endothelial cells accompanied by EHT and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA signalling or BMP, WNT, NOTCH signalling interrupted this reprogramming event. This partnership between endothelial cells and AGM Mesp1der PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.

developmental biology↗

bioRxiv2020

Label-free Isolation and Single Cell Biophysical Phenotyping Analysis of Primary Cardiomyocytes using Inertial Microfluidics

To advance our understanding of cardiomyocyte identity and function, we need appropriate tools to isolate pure primary cardiomyocytes. We have developed a label-free method to purify viable cardiomyocytes from mouse neonatal hearts using a simple inertial microfluidics biochip. Cardiomyocytes were sorted from neonatal hearts and isolated to >90% purity and their physico-mechanical properties were evaluated using real time deformability cytometry. Purified cardiomyocytes were viable and retained their identity and function as depicted by expression of cardiac specific markers and contractility. Furthermore, we showed that cardiomyocytes have a distinct physico-mechanical phenotype that could be used as an intrinsic biophysical marker to distinguish these cells from other cell types within the heart. Taken together, this cardiomyocyte isolation and phenotyping method could serve as a valuable tool to progress our understanding of cardiomyocyte identity and function, which will ultimately benefit many diagnostic development and cardiac treatment studies.

bioengineering↗

bioRxiv2020

Capturing Neonatal Cardiomyocyte - Endothelial interactions on-a-Chip

The neonatal heart has been the focus of numerous investigations due to its inherent regenerative potential. However, the interactions between neonatal cardiomyocytes (CMs) and endothelial cells (ECs) have been difficult to model and study due to the lack of an appropriate device. Here, we developed a method to culture primary neonatal CMs and ECs in a microchip and characterise their behavioural properties over a 14-day period. By implementing cell migration analyses coupled with immunostaining and confocal microscopy, we were able to identify and quantify sub-populations of migratory and non-migratory ECs. In CM-EC co-cultures, migrating ECs were found to move in higher numbers and longer distances compared to migrating CMs. In the presence of CMs, non-migrating ECs established connexin gap junctions and formed CM-EC cell aggregates, which were likely a priming event for endothelial organoid formation. This microfluidic device also enabled us to visualise the temporal sequence organoid formation and phenomena such as collective cell migration, CM-EC trans-differentiation and synchronisation of CM beating. This microchip based culture system has potential applications for tissue engineering and drug discovery.

bioengineering↗