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Communications Biology Oct 2022The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However,...
The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However, direct comparison of hepatocyte models is currently challenging. We systematically searched the literature and compared different HLCs, but reported functions were limited to a small subset of hepatic functions. To enable a more comprehensive comparison, we developed an algorithm to compare transcriptomic data across studies that tested HLCs derived from hepatocytes, biliary cells, fibroblasts, and pluripotent stem cells, alongside primary human hepatocytes (PHHs). This revealed that no HLC covered the complete hepatic transcriptome, highlighting the importance of HLC selection. HLCs derived from hepatocytes had the highest transcriptional resemblance to PHHs regardless of the protocol, whereas the quality of fibroblasts and PSC derived HLCs varied depending on the protocol used. Finally, we developed and validated a web application (HLCompR) enabling comparison for specific pathways and addition of new HLCs. In conclusion, our comprehensive transcriptomic comparison of HLCs allows selection of HLCs for specific research questions and can guide improvements in culturing conditions.
Topics: Cell Differentiation; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Transcriptome
PubMed: 36241695
DOI: 10.1038/s42003-022-04046-9 -
World Journal of Transplantation Mar 2020Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies...
BACKGROUND
Orthotopic liver transplantation (OLT) is the only treatment for end-stage liver failure; however, graft shortage impedes its applicability. Therefore, studies investigating alternative therapies are plenty. Nevertheless, no study has comprehensively analyzed these therapies from different perspectives.
AIM
To summarize the current status of alternative transplantation therapies for OLT and to support future research.
METHODS
A systematic literature search was performed using PubMed, Cochrane Library and EMBASE for articles published between January 2010 and 2018, using the following MeSH terms: [(liver transplantation) AND cell] OR [(liver transplantation) AND differentiation] OR [(liver transplantation) AND organoid] OR [(liver transplantation) AND xenotransplantation]. Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation. Among them, we selected articles including transplantation.
RESULTS
A total of 89 studies were selected. There are three principle forms of treatment for liver failure: Xeno-organ transplantation, scaffold-based transplantation, and cell transplantation. Xeno-organ transplantation was covered in 14 articles, scaffold-based transplantation was discussed in 22 articles, and cell transplantation was discussed in 53 articles. Various types of alternative therapies were discussed: Organ liver, 25 articles; adult hepatocytes, 31 articles; fetal hepatocytes, three articles; mesenchymal stem cells (MSCs), 25 articles; embryonic stem cells, one article; and induced pluripotent stem cells, three articles and other sources. Clinical applications were discussed in 12 studies: Cell transplantation using hepatocytes in four studies, five studies using umbilical cord-derived MSCs, three studies using bone marrow-derived MSCs, and two studies using hematopoietic stem cells.
CONCLUSION
The clinical applications are present only for cell transplantation. Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations, which warrants future research to find relevant clinical applications.
PubMed: 32257850
DOI: 10.5500/wjt.v10.i3.64 -
Annals of Hematology May 2020Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital...
Fanconi anemia (FA) is a DNA repair disorder resulting from mutations in genes encoding for FA DNA repair complex components and is characterized by variable congenital abnormalities, bone marrow failure (BMF), and high incidences of malignancies. FA mosaicism arises from reversion or other compensatory mutations in hematopoietic cells and may be associated with BMF reversal and decreased blood cell sensitivity to DNA-damaging agents (clastogens); this sensitivity is a phenotypic and diagnostic hallmark of FA. Uncertainty regarding the clinical significance of FA mosaicism persists; in some cases, patients have survived multiple decades without BMF or hematologic malignancy, and in others hematologic failure occurred despite the presence of clastogen-resistant cell populations. Assessment of mosaicism is further complicated because clinical evaluation is frequently based on clastogen resistance in lymphocytes, which may arise from reversion events both in lymphoid-specific lineages and in more pluripotent hematopoietic stem/progenitor cells (HSPCs). In this review, we describe diagnostic methods and outcomes in published mosaicism series, including the substantial intervals (1-6 years) over which blood counts normalized, and the relatively favorable clinical course in cases where clastogen resistance was demonstrated in bone marrow progenitors. We also analyzed published FA mosaic cases with emphasis on long-term clinical outcomes when blood count normalization was identified. Blood count normalization in FA mosaicism likely arises from reversion events in long-term primitive HSPCs and is associated with low incidences of BMF or hematologic malignancy. These observations have ramifications for current investigational therapeutic programs in FA intended to enable gene correction in long-term repopulating HSPCs.
Topics: Bone Marrow Cells; Fanconi Anemia; Hematologic Neoplasms; Hematopoietic Stem Cells; Humans; Mosaicism
PubMed: 32065290
DOI: 10.1007/s00277-020-03954-2 -
Frontiers in Endocrinology 2022Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion...
BACKGROUND
Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion of patients suffer from persisting complaints due to unbalanced hormone levels, leaving room for new therapeutic strategies, such as tissue engineering and regenerative medicine.
METHODS
Electronic searches of databases for studies of thyroid regeneration or thyroid organoids were performed. A systematic review including both and models of thyroid regenerative medicine was conducted.
RESULTS
Sixty-six independent studies published between 1959 and May 1st, 2022 were included in the current systematic review. Among these 66 studies, the most commonly involved species was human (19 studies), followed by mouse (18 studies), swine (14 studies), rat (13 studies), calf/bovine (4 studies), sheep/lamb (4 studies) and chick (1 study). In addition, in these experiments, the most frequently utilized tissue source was adult thyroid tissue (46 studies), followed by embryonic stem cells (ESCs)/pluripotent stem cells (iPSCs) (10 studies), rat thyroid cell lines (7 studies), embryonic thyroid tissue (2 studies) and newborn or fetal thyroid tissue (2 studies). Sixty-three studies reported relevant thyroid follicular regeneration experiments , while 21 studies showed an experiment section that included transplanting engineered thyroid tissue into recipients. Together, 12 studies were carried out using 2D structures, while 50 studies constructed 3D structures.
CONCLUSIONS
Each aspect of thyroid regenerative medicine was comprehensively described in this review. The recovery of optimal hormonal equilibrium by the transplantation of an engineered functional thyroid holds great therapeutic promise.
Topics: Animals; Humans; Sheep; Cattle; Mice; Rats; Swine; Hypothyroidism; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Hormones
PubMed: 36531472
DOI: 10.3389/fendo.2022.1065410