Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture

Ong, Shin-Yeu; Dai, Hui; Leong, Kam W.

doi:10.1016/j.biomaterials.2006.03.022

Cited by 136 publications

(109 citation statements)

References 43 publications

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“…For instance, Hildebrandt et al (2011), by using the von Kossa staining proved the osteogenic differentiation of MSC spheroids after 35 days of cultivation. Similarly, Ong et al (2006) investigated the differentiation ability of human MSC spheroids into hepatocytes, and after for 4 weeks of differentiation they implanted the spheroids into the liver of hepatectomized rats to assess the engraftment potential of these transdifferentiated cells. Longer term studies were performed by Mauck et al (2006) that analysed the chondrogeninc differentiation ability of bovine MSC over a 10-week period.…”

Section: Introductionmentioning

confidence: 99%

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

et al. 2016

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Three-dimensional (3D) spheroids of mesenchymal stromal cells (MSC) have been demonstrated to improve a wide range of MSC features, such as multilineage potential, secretion of therapeutic factors, and resistance against hypoxic condition. Accordingly, they represent a promising tool in regenerative medicine for several biological and clinical applications. Many approaches have been proposed to generate MSC spheroids. They usually require specific generation systems, such as rotatory bioreactors or low-attachment plates, and each approach has its own disadvantages. Furthermore, an over-time analysis of morphological homogeneity and architectural stability of the spheroids generated is rarely provided. In this work we adapted the ''pellet culture'' method to obtain homogenous spheroids of MSC and maintain them in vitro for long term studies. We analysed their outer and inner structure over a 2-month period to provide morphological and architectural information regarding the spheroids generated. Quantitative and qualitative data were obtained using brightfield and confocal microscope imaging coupled to a computational analysis to estimate volume, sphericity, and jagging degree. In addition, histological evaluation was performed to more thoroughly assess the cellular composition and the internal architecture of the 3D spheroids. The results provided show that MSC spheroids generated with the proposed approach are homogeneous and stable, from both morphological and architectural points of view, for a period of at least 15 days, approximately between day 15 and day 30 after their generation. Accordingly, the approach proposed serves as a rapid, cost-effective, and efficient method to generate and maintain MSC spheroids using common entry-level laboratory equipment only.Keywords Mesenchymal stromal/stem cells Á 3D multicellular spheroids Á Pellet culture method Á Morphological analysis Á Microscopy Á Computational analysis Chiara Bellotti and Serena Duchi contributed equally to this work.

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Section: Introductionmentioning

confidence: 99%

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

et al. 2016

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“…Thus, it is worth exploring whether such positive effects of 3D cultivation translate to the differentiation of stem cells to hepatocyte-like cells. Differentiation to the hepatic lineage in 3D culture has been attempted using both ESC 23,24 and mesenchymal stem cells 25,26 with encouraging results. However, those early studies were performed with singlestep protocols, not with the multistep directed differentiation methods that have been employed recently with more success.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Differentiation of Adult Bone Marrow-Derived Stem Cells to Liver Lineage in Aggregate Culture

Subramanian

Owens

O’Brien

et al. 2011

Tissue Engineering Part A

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Hepatocyte-like cells derived from stem cells hold great potential for clinical and pharmaceutical applications, including high-throughput drug toxicity screening. We report a three-dimensional aggregate culture system for the directed differentiation of adult rat bone marrow-derived stem cells, rat multipotent adult progenitor cells, to hepatocyte-like cells. Compared to adherent monolayer cultures, differentiation in the aggregate culture system resulted in significantly higher expression level of liver-specific transcripts, including an increased albumin mRNA level, and higher levels of albumin and urea secretion. This coincides with the presence of significantly more cells that express intracellular albumin at levels found in primary hepatocytes. The differentiated cell aggregates exhibited cytochrome P450-mediated ethoxyresorufin-O-dealkylation and pentoxyresorufin-O-dealkylation activity. Consistent with these increased mature functions, cells within the aggregates were shown to have many ultrastructural features of mature hepatocytes by transmission electron microscopy. With the scalability of the aggregate culture system and the enhanced differentiation capability, this system may facilitate translation of generating hepatocytes from stem cells to technology.

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“…4 ES cells have enormous potential; however, many limitations, such as teratoma formation followed by tumor genesis, immunogenicity, and ethical issues, are arresting their clinical usage. Adult human stem cells are promising candidates for liver regeneration, [5][6][7][8][9][10] and their usage might sidestep obstacles, such as ethical concerns and risks of rejection. Currently, the focus is on mesenchymal stem cells (MSCs), found in human bone marrow (BM), 11 adipose tissue (AT), 12,13 scalp tissue, 14 placenta, 15 and umbilical cord blood (UCB) 16 as well as in various fetal tissues.…”

mentioning

confidence: 99%

Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes

Banas¹,

Teratani²,

et al. 2007

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Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture

Cited by 136 publications

References 43 publications

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

Enhanced Differentiation of Adult Bone Marrow-Derived Stem Cells to Liver Lineage in Aggregate Culture

Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes

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