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Table of Contents
JOURNAL SCAN
Year : 2018  |  Volume : 7  |  Issue : 3  |  Page : 153-154

Journal scan


Provenance and Peer Review Commissioned; Internally Peer Reviewed

Date of Web Publication8-Apr-2019

Correspondence Address:
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_4_19

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How to cite this article:
Suresh V, Bitla A R. Journal scan. J Clin Sci Res 2018;7:153-4

How to cite this URL:
Suresh V, Bitla A R. Journal scan. J Clin Sci Res [serial online] 2018 [cited 2019 Apr 22];7:153-4. Available from: http://www.jcsr.co.in/text.asp?2018/7/3/153/255666



Development of liver decellularised extracellular matrix bioink for three-dimensional cell printing-based liver tissue engineering

The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liverin vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimised for 3D-cell printing-based liver tissue engineering remains. The authors thus developed a liver decellularised extracellular matrix (dECM) bioink for 3D-cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D-cell printing. The authors further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated. The liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results of this study demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D-cell printing-based liver tissue engineering.


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Bioprint is a process to refabricate tissues (3D tissue) using synthetic or natural materials with bioinks (cells or biomolecules). 3D-tissue models create a physiologically relevant 3D-model platform to build tissue-like or organ-like miniatures. In this article, Lee et al. developed liver dECM bioink for 3D-cell printing. The liver dECM bioink-enhanced stem cell differentiation and HepG2-cell functions. The models are useful for drug development, and to model biological processes, such as tissue development and disease.

Lee H, Han W, Kim H, Ha DH, Jang J, Kim BS, et al. Development of liver decellularized extracellular matrix bioink for three-dimensional cell printing-based liver tissue engineering. Biomacromolecules 2017;18:1229-37.

Breast cancer chemo-immunotherapy through liposomal delivery of an immunogenic cell death stimulus plus interference in the indoleamine 2,3-dioxygenase pathway

39Immunotherapy provides the best approach to reduce the high mortality of metastatic breast cancer (BC). In this study, the authors demonstrate a chemoimmunotherapy approach for breast cancer, using a dual-drug delivery liposomal carrier that introduces an immunogenic cell death stimulus while, at the same time also interferes in the regionally overexpressed indoleamine 2,3-dioxygenase (IDO1) pathway that prevents effective T-cell priming. The liposome was constructed by self-assembly of a phospholipid-conjugated prodrug, indoximod (IND), which inhibits the IDO1 pathway, followed by the remote loading of the ICD-inducing chemo drug, doxorubicin (DOX). Intravenous injection of the encapsulated two-drug combination dramatically improved the pharmacokinetics and tumour drug concentrations of DOX and IND in an orthotopic 4T1 tumour model in syngeneic mice. Delivery of a threshold ICD stimulus resulted in the uptake of dying BC cells by dendritic cells, tumour antigen presentation and the activation/recruitment of naïve T-cells. The subsequent activation of perforin- and IFN-γ releasing cytotoxic T-cells (CTLs)-induced robust tumour cell killing at the primary as well as metastatic tumour sites. Immune phenotyping of the tumour tissues confirmed the recruitment of CD8+ CTLs, disappearance of Tregs and an increase in CD8+/FOXP3+ T-cell ratios. Not only does the DOX/IND-Liposome provide a synergistic antitumor response that is superior to a DOX-only liposome, but it also demonstrated that the carrier could be effectively combined with PD-1 blocking antibodies to eradicate lung metastases. All considered, an innovative nano-enabled approach has been established to allow deliberate use of ICD to switch an immune deplete to an immune replete BC microenvironment, allowing further boosting of the response by co-administered IDO inhibitors or immune checkpoint blocking antibodies.


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Lu et al. elucidated the advantage of combining chemotherapy and immunotherapy by developing liposomal dual drug delivery system to control metastatic breast cancer. The dual drug namely DOX initiates calreticulin pathway leading to tumour cell engulfment by macrophages while IND inhibits IDO-I pathway or the activation of CD8 + cells responsible for BC metastases. The significance of the present pre-clinical study of synergistic drug combination is hope for possible clinical translation in human breast cancer.

Lu J, Liu X, Liao YP, Wang X, Ahmed A, Jiang W, et al. Breast cancer chemo-immunotherapy through liposomal delivery of an immunogenic cell death stimulus plus interference in the IDO-1 pathway. ACS Nano 2018;12:11041-61.

Polymer − Temozolomide conjugates as therapeutics for treating glioblastoma

A series of polymer-drug conjugates based on 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared with the glioblastoma drug temozolomide (TMZ) as pendent groups. Random and block copolymers were synthesised by reversible addition − fragmentation chain-transfer polymerisation using a TMZ-containing methacrylate monomer. In the present study, the solution properties of the polyMPC − TMZ copolymers were investigated by dynamic light scattering and transmission electron microscopy, revealing well-defined nanostructures from the block copolymers. Conjugation of TMZ to polyMPC enhanced drug stability, with decomposition half-life values ranging from 2 to 19 times longer than that of free TMZ. The cytotoxicity of polyMPC − TMZ was evaluated in both chemosensitive (U87MG) and chemoresistant (T98G) glioblastoma cell lines. Furthermore, the polyMPC − TMZ platform was expanded considerably by the preparation of redox-sensitive polyMPC − TMZ copolymers utilising disulfides as the polymer-to-drug linker.


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Glioblastoma is a solid tumour of non-neuronal glial cells of the brain. Owing to its aggressive nature, it is treated using a regimen of surgery, radiation and chemotherapy. Recurrences despite the demonstrated benefits of combination therapy are overwhelmingly making treatment challenging. In the present work, Ward et al. synthesised the polyMPC − olyMPC sized t. This polymer − drug platform was enhanced by incorporating redox-sensitive linkers between the polymer and drug. The efficacy of this conjugate was tested in chemosensitive and chemoresistant glioblastoma cell lines. The promising results from this study show that these conjugates can be applied to various diseases which enhance drug pharmacokinetics leading to better therapeutic outcomes with reduced potential side effects.

Ward SM, Skinner M, Saha B, Emrick T. Polymer-temozolomide conjugates as therapeutics for treating glioblastoma. Mol Pharm 2018;15:5263-76.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.






 

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