Human hepatocyte transplantation has been actively perused as an alternative to liver replacement for acute liver failure and liver-based metabolic defects. Current challenges in this field include a limited cell source, reduced cell viability following cryopreservation and poor engraftment of cells into the recipient liver with consequent limited life span. As a result, alternative stem cell sources such as pluripotent stem cells, fibroblasts, hepatic progenitor cells, amniotic epithelial cells and mesenchymal stem/stromal cells (MSCs) can be used to generate induced hepatocyte like cells (HLC) with each technique exhibiting advantages and disadvantages. HLCs may have comparable function to primary human hepatocytes and could offer patient-specific treatment. However, long-term functionality of transplanted HLCs and the potential oncogenic risks of using stem cells have yet to be established. The immunomodulatory effects of MSCs are promising, and multiple clinical trials are investigating their effect in cirrhosis and acute liver failure. Here, we review the current status of hepatocyte transplantation, alternative cell sources to primary human hepatocytes and their potential in liver regeneration. We also describe recent clinical trials using hepatocytes derived from stem cells and their role in improving the phenotype of several liver diseases.

journal article

Open Access Collection

Electron cryomicroscopy as a powerful tool in biomedical research

Quentin, Dennis; Raunser, Stefan

2018 Journal of Molecular Medicine

doi: 10.1007/s00109-018-1640-ypmid: 29730699

A human cell is a precisely regulated system that relies on the complex interaction of molecules. Structural insights into the cellular machinery at the atomic level allow us to understand the underlying regulatory mechanism and provide us with a roadmap for the development of novel drugs to fight diseases. Facilitated by recent technological breakthroughs, the Nobel prize-winning technique electron cryomicroscopy (cryo-EM) has become a versatile and extremely powerful tool to solve routinely near-atomic resolution three-dimensional protein structures. Consequently, it has become the focus of attention for structure-based drug design. In this review, we describe the basics of cryo-EM and highlight its growing role in biomedical research. Furthermore, we discuss latest developments as well as future perspectives.

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LitStream Collection

CUL4B promotes the pathology of adjuvant-induced arthritis in rats through the canonical Wnt signaling

Miao, Chenggui; Chang, Jun; Zhang, Guoxue; Yu, Hao; Zhou, Lili; Zhou, Guoliang; Zhao, Chuanlei

2018 Journal of Molecular Medicine

doi: 10.1007/s00109-018-1635-8pmid: 29626254

journal article

LitStream Collection

Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1

Jin, Shufang; Ma, Hailong; Yang, Wenyi; Ju, Houyu; Wang, Lizhen; Zhang, Zhiyuan

2018 Journal of Molecular Medicine

doi: 10.1007/s00109-018-1636-7pmid: 29713760

Cell division cycle 7 (Cdc7) plays important roles in the regulation of the initiation of DNA replication throughout S phase. Whether inhibition of Cdc7 has a direct antitumour effect in oral squamous cell carcinoma (OSCC) remains unclear. In this study, XL413, a novel Cdc7 inhibitor, markedly inhibited the viability of OSCC cells but not that of non-tumour primary cells. There was a synergistic effect between XL413 and DNA-damaging agents (e.g. cisplatin and 5-fluorouracil) on OSCC in vitro and in vivo. Moreover, XL413 exhibited a notable antitumour effect on OSCC patients with high Cdc7 expression in mini patient-derived xenografts model. The proliferation was significantly inhibited in OSCC cells after Cdc7 silencing. Cdc7 knockdown significantly induced apoptosis in OSCC cell lines. Furthermore, we demonstrated that Cdc7 was overexpressed and transcriptionally regulated by E2F1 in OSCC by using chromatin immunoprecipitation and luciferase assays. Our results reveal that XL413 has an excellent antitumour effect in OSCC. Importantly, it does not inhibit the proliferation of non-tumour cells. These findings suggest that the overexpression of Cdc7 promotes progression in OSCC and that inhibition of Cdc7 is a very promising therapy for OSCC patients.

journal article

LitStream Collection

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018 Journal of Molecular Medicine

doi: 10.1007/s00109-018-1643-8pmid: 29725737

journal article

Open Access Collection

Psoriasin, a novel anti-Candida albicans adhesin

Brauner, Annelie; Alvendal, Cathrin; Chromek, Milan; Stopsack, Konrad; Ehrström, Sophia; Schröder, Jens; Bohm-Starke, Nina

2018 Journal of Molecular Medicine

doi: 10.1007/s00109-018-1637-6pmid: 29736603