Hepatogenic Potential of Human Bone Marrow and Umbilical Cord Blood Mesenchymal Stem Cells

Kosmacheva, S. M.; Seviaryn, Ihar; Гончарова, Н. В.; Petyovka, N. V.; Потапнев, М. П.

doi:10.1007/s10517-011-1276-1

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…The stage-specific temporal gene and protein expression profiles of our hiPSC-EB-HLCs are consistent with previous reports 66 67 68 69 70 71 , confirming a stepwise differentiation into mature hepatocytes using our protocol. Our protocol recapitulates in vitro the four stages seen in liver development during normal embryogenesis, starting with the pluripotent state (PS), definitive endoderm (DE), foregut endoderm (FE), hepatic progenitors or hepatoblast (HP), and mature hepatocytes (MH).…”

Section: Discussionsupporting

confidence: 91%

“…2D differentiation on planar substrates fails to capture the intricate structure of the 3D extracellular environment in native tissue, and therefore constrains the ability to generate cells of phenotypes and properties that closely mimic primary cells in vivo . During liver organogenesis, the liver bud is a 3D structure with dynamic cell-cell interactions among multiple cell types during development 66 67 68 69 70 71 . Cell-cell interactions, particularly through E-cadherin positively impact hepatocyte maturation 72 73 .…”

Section: Discussionmentioning

confidence: 99%

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Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition

Pettinato

Ramanathan

Fisher

et al. 2016

Sci Rep

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Treatment of acute liver failure by cell transplantation is hindered by a shortage of human hepatocytes. Current protocols for hepatic differentiation of human induced pluripotent stem cells (hiPSCs) result in low yields, cellular heterogeneity, and limited scalability. In the present study, we have developed a novel multicellular spheroid-based hepatic differentiation protocol starting from embryoid bodies of hiPSCs (hiPSC-EBs) for robust mass production of human hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway. The resultant hiPSC-EB-HLCs expressed liver-specific genes, secreted hepatic proteins such as Albumin, Alpha Fetoprotein, and Fibrinogen, metabolized ammonia, and displayed cytochrome P450 activities and functional activities typical of mature primary hepatocytes, such as LDL storage and uptake, ICG uptake and release, and glycogen storage. Cell transplantation of hiPSC-EB-HLC in a rat model of acute liver failure significantly prolonged the mean survival time and resolved the liver injury when compared to the no-transplantation control animals. The transplanted hiPSC-EB-HLCs secreted human albumin into the host plasma throughout the examination period (2 weeks). Transplantation successfully bridged the animals through the critical period for survival after acute liver failure, providing promising clues of integration and full in vivo functionality of these cells after treatment with WIF-1 and DKK-1.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition

Pettinato

Ramanathan

Fisher

et al. 2016

Sci Rep

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“…However, in most cases, these organoids lack any endothelial component, which represents an important part of liver organogenesis in vivo [10,11]. Nonetheless, the broader application of hiPSC-derived liver organoids demands better scalability, an improved post-differentiation phenotype, and proven long-term function both in vitro and in vivo [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components

Ietto

Iori

Gritti

et al. 2023

Cells

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Over 40,000 patients in the United States are estimated to suffer from end-stage liver disease and acute hepatic failure, for which liver transplantation is the only available therapy. Human primary hepatocytes (HPH) have not been employed as a therapeutic tool due to the difficulty in growing and expanding them in vitro, their sensitivity to cold temperatures, and tendency to dedifferentiate following two-dimensional culture. The differentiation of human-induced pluripotent stem cells (hiPSCs) into liver organoids (LO) has emerged as a potential alternative to orthotropic liver transplantation (OLT). However, several factors limit the efficiency of liver differentiation from hiPSCs, including a low proportion of differentiated cells capable of reaching a mature phenotype, the poor reproducibility of existing differentiation protocols, and insufficient long-term viability in vitro and in vivo. This review will analyze various methodologies being developed to improve hepatic differentiation from hiPSCs into liver organoids, paying particular attention to the use of endothelial cells as supportive cells for their further maturation. Here, we demonstrate why differentiated liver organoids can be used as a research tool for drug testing and disease modeling, or employed as a bridge for liver transplantation following liver failure.

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Production of Good Manufacturing Practice-Grade Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Therapeutic Use

Pham

Phan

2014

Methods in Molecular Biology

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Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are multipotent stem cells that can be differentiated into several specific cell types such as adipocytes, osteoblasts, and chondroblasts. They also were demonstrated to trans-differentiate into other cell lineages such as muscle cells and neurons. Thus, they are considered a promising stem cell source for therapeutic use. Here, we describe a method for production of good manufacturing practice-grade human UCB-MSCs for therapeutic use. The obtained UCB-MSCs are free of allogenous or xenogenous proteins. In addition, these MSCs could maintain the MSC phenotype in long-term culture.

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Hepatogenic Potential of Human Bone Marrow and Umbilical Cord Blood Mesenchymal Stem Cells

Cited by 6 publications

References 14 publications

Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition

Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition

Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components

Production of Good Manufacturing Practice-Grade Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Therapeutic Use

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