scholarly journals Robust Expansion and Functional Maturation of Human Hepatoblasts by Chemical Strategy

Author(s):  
Tingcai Pan ◽  
Jiawang Tao ◽  
Yan Chen ◽  
Jiaye Zhang ◽  
Anteneh Getachew ◽  
...  

Abstract Background: Chemically strategies to generate hepatic cells from human pluripotent stem cells (hPSCs) for the potential clinical application have been improved. However, producing high quality and large quantities of hepatic cells remain challenging, especially in terms of step-wise efficacy and cost-effective production requires more improvements. Methods: Here, we systematically evaluated chemical compounds for hepatoblasts (HBs) expansion and maturation to establish a robust, cost-effective and reproducible methodology for self-renewal HBs and functional hepatocyte-like cells (HLCs) production. Results: The established chemical cocktail could enable HBs to proliferate nearly 3000 folds within 3 weeks with preserved bipotency. Moreover, those expanded HBs could be further efficiently differentiated into homogenous HLCs displayed typical morphologic and functionality as mature hepatocytes, including hepatocyte identity markers expression and key functional activities such as cytochrome P450 metabolism activities and urea secretion. Importantly, the transplanted HBs in injured liver of immune-defect mice differentiated as hepatocytes, engraft and repopulate in the injured loci of the recipient liver. Conclusion: Together, this chemical compound based HLCs generation method presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery application.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tingcai Pan ◽  
Jiawang Tao ◽  
Yan Chen ◽  
Jiaye Zhang ◽  
Anteneh Getachew ◽  
...  

Abstract Background Chemically strategies to generate hepatic cells from human pluripotent stem cells (hPSCs) for the potential clinical application have been improved. However, producing high quality and large quantities of hepatic cells remain challenging, especially in terms of step-wise efficacy and cost-effective production requires more improvements. Methods Here, we systematically evaluated chemical compounds for hepatoblast (HB) expansion and maturation to establish a robust, cost-effective, and reproducible methodology for self-renewal HBs and functional hepatocyte-like cell (HLC) production. Results The established chemical cocktail could enable HBs to proliferate nearly 3000 folds within 3 weeks with preserved bipotency. Moreover, those expanded HBs could be further efficiently differentiated into homogenous HLCs which displayed typical morphologic features and functionality as mature hepatocytes including hepatocyte identity marker expression and key functional activities such as cytochrome P450 metabolism activities and urea secretion. Importantly, the transplanted HBs in the injured liver of immune-defect mice differentiated as hepatocytes, engraft, and repopulate in the injured loci of the recipient liver. Conclusion Together, this chemical compound-based HLC generation method presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery application.


2020 ◽  
Author(s):  
Götz Laible ◽  
Sally Cole ◽  
Brigid Brophy ◽  
Paul Maclean ◽  
Li How Chen ◽  
...  

ABSTRACTTherapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for enhanced effectiveness and better safety profile compared to treatments with Erbitux. In addition, our study validates transgenic goats as an excellent platform for large-scale production of therapeutic mAbs.


2013 ◽  
Vol 2013 (DPC) ◽  
pp. 000377-000397
Author(s):  
Jon G. Aday ◽  
Ted Tessier ◽  
Kazuhisa Itoi ◽  
Satoshi Okude

Embedded die substrate technologies are being developed in an assortment of configurations and for different market segments. The technology being discussed in this paper will be focused on both a fan out technology – ChipsetT Fan-Out and a system in package approach (ChipsetT SiP) in which a multiple component bill of materials (BOM) is used. The Chipset process is based on the WABE (Wafer and Board Level Embedding) technology. WABE technology is based on co-lamination of multilayer polyimide flex wiring and conductive z-axis sintered metal interconnections. This ChipsetT Fan Out technology allows for large scale production of fan out type solutions which can allow for very thin packages in addition to unique pin out solutions such as pin compatibility for a competitor part. The ChipsetT SiP also allows embedding of single or multiple silicon die and/or components. Additional components can also be placed using conventional SMT on the top or bottom side of the package. There is a great deal of design flexibility with this technology which makes it a great solution for applications trying to reduce their x-y size or z-height. When utilizing RDL technology on the embedded die we are able to do the fine pitch routing in order to allow the substrate to route at larger pitches ensuring an overall cost effective solution. This paper will focus on the different classes of applications that have benefited from this technology and will discuss the benefits and tradeoffs of the different solutions that have been engineered. Assembly and reliability data will be presented on several of the applications showing a robust solution set.


2019 ◽  
Vol 21 (2) ◽  
pp. 198-204 ◽  
Author(s):  
Kaiyu Xie ◽  
Ali Reza Kamali

Molten salt electrolytic reduction of Fe2O3 in the presence of water is proposed as a sustainable and cost-effective approach for large-scale production of iron.


2007 ◽  
Vol 534-536 ◽  
pp. 773-776
Author(s):  
R. Cook ◽  
I.T.H. Chang ◽  
C. Lucien Falticeanu

P/M aluminium components are attracting interest in an increasing variety of industries due to the possibilities for weight saving in engineering parts. There are many processes for manufacturing from powder feedstocks that are either in production, becoming commercialised or still undergoing development. The nature of these processes and the required properties of the end products mean that powders of different particle size, shape, composition and microstructure must be produced. The requirements of various processes requiring aluminium and aluminium alloy powders for metal matrix composites, laser sintering, powder forging and metal injection moulding are discussed in relation to powder particle size and structure. The key requirement of the powder manufacturer is to supply cost effective materials for these different processes. This may require compromises to be made by the supplier and consumer while the techniques evolve from development to large scale production.


Catalysts ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 60
Author(s):  
Muhammad Amtiaz Nadeem ◽  
Mohd Adnan Khan ◽  
Ahmed Abdeslam Ziani ◽  
Hicham Idriss

The conversion of solar to chemical energy is one of the central processes considered in the emerging renewable energy economy. Hydrogen production from water splitting over particulate semiconductor catalysts has often been proposed as a simple and a cost-effective method for large-scale production. In this review, we summarize the basic concepts of the overall water splitting (in the absence of sacrificial agents) using particulate photocatalysts, with a focus on their synthetic methods and the role of the so-called “co-catalysts”. Then, a focus is then given on improving light absorption in which the Z-scheme concept and the overall system efficiency are discussed. A section on reactor design and cost of the overall technology is given, where the possibility of the different technologies to be deployed at a commercial scale and the considerable challenges ahead are discussed. To date, the highest reported efficiency of any of these systems is at least one order of magnitude lower than that deserving consideration for practical applications.


2021 ◽  
Vol 34 (3) ◽  
Author(s):  
ELMER G. VILLANUEVA ◽  
KYRA HOEVENAARS ◽  
JONAH VAN BEIJNEN ◽  
AL P. GONZALES ◽  
LOTA A. CREENCIA ◽  
...  

Three hatchery experiments for orange-spotted spinefoot, Siganus guttatus (Bloch, 1787), were carried out in Puerto Princesa City, Palawan, Philippines using larvae and fingerlings produced through induced spawning. The first experiment (E1) involving larvae raised in six 5,000-L concrete tanks until 39 days post-hatch (dph) comparing two stocking densities (T1: 3; and T2: 5 larva.L-1), obtained survival rates (SR) of 6.00 and 7.85 %. The second experiment (E2) monitored the growth and survival of 47 dph juveniles for 3 weeks, raised in 25-L plastic basins, fed with a commercial diet at three stocking densities with five replications. The initial stocking densities (6, 12, 18 ind.L-1) were reduced during the second (4, 8, 12 ind.L-1) and third (2, 4, 6 ind.L-1) week, respectively. The weekly SR for all treatments ranged between 99.2 and 100 %. Weekly final total lengths (TL) were not significantly different except during the second week. The third experiment (E3) evaluated the effects of two types of commercial feeds (T1: grouper feed; T2: milkfish feed) on the growth and survival of 47 dph juveniles in plastic basins for 3 weeks, at similar densities reduced on a weekly basis. The SR (96.2 to 99.9 %) were not significantly different, but the TL of fish in T1 (4.39 cm) were significantly bigger than in T2 (3.52 cm). While there is a need to improve the low and irregular survival of S. guttatus larvae for cost-effective large-scale production, we recommend using small basins in the intensive rearing of juveniles.


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