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Abstract Bone marrow derived mesenchymal stem cells (BM‐MSC) is a promising alternative cell source to primary hepatocytes because of their ability to differentiate into hepatocyte‐like cells. However, their inability to differentiate efficiently and potential to turn into myofibroblasts restrict their applications. This study developed a plate coating from the liver extracellular matrix (ECM) and investigated its ability in facilitating the BM‐MSCs proliferation, hepatic differentiation, and hepatocyte‐specific functions duringin vitroculture. After 28‐day culture, BM‐MSCs on the ECM coating showed hepatocyte‐like morphology, and certain cells took up low‐density lipoprotein. Synthesis of albumin, urea, and anti‐alpha‐fetoprotein, as well as expression of certain hepatic markers, in cells cultured on ECM were higher than cells cultured on non‐coated and Matrigel‐coated plates. mRNA levels of CYP3A4, albumin, CK18, and CYP7A1 in cells on ECM coating were significantly higher than cells cultured on the non‐coating environment. In conclusion, viability and hepatogenic differentiation of BM‐MSCs cultured on both Matrigel and ECM coating were significantly enhanced compared with those cultured on non‐coated plates. Moreover, the liver ECM coating induced additional metabolic functions relative to the Matrigel coating. The liver ECM hydrogel preserves the natural composition, promotes simple gelling, induces efficient stem cell hepatogenic differentiation, and may have uses as an injectable intermedium for hepatocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 829–838, 2018.
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Spatial subcellular organelle networks in single cells
Abstract Organelles play important roles in human health and disease, such as maintaining homeostasis, regulating growth and aging, and generating energy. Organelle diversity in cells not only exists between cell types but also between individual cells. Therefore, studying the distribution of organelles at the single-cell level is important to understand cellular function. Mesenchymal stem cells are multipotent cells that have been explored as a therapeutic method for treating a variety of diseases. Studying how organelles are structured in these cells can answer questions about their characteristics and potential. Herein, rapid multiplexed immunofluorescence (RapMIF) was performed to understand the spatial organization of 10 organelle proteins and the interactions between them in the bone marrow (BM) and umbilical cord (UC) mesenchymal stem cells (MSCs). Spatial correlations, colocalization, clustering, statistical tests, texture, and morphological analyses were conducted at the single cell level, shedding light onto the interrelations between the organelles and comparisons of the two MSC subtypes. Such analytics toolsets indicated that UC MSCs exhibited higher organelle expression and spatially spread distribution of mitochondria accompanied by several other organelles compared to BM MSCs. This data-driven single-cell approach provided by rapid subcellular proteomic imaging enables personalized stem cell therapeutics.
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- Award ID(s):
- 1648035
- PAR ID:
- 10522394
- Publisher / Repository:
- Nature
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41598-023-32474-y
