Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

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Human T-cell leukemia virus type 1 (HTLV-1) induces cell proliferation after infection, leading to efficient transmission by cell-to-cell contact. After a long latent period, a fraction of carriers develop adult T-cell leukemia (ATL). Genetic changes in the tax gene in ATL cells were reported in about 10% of ATL cases. To determine genetic changes that may occur throughout the provirus, we determined the entire sequence of the HTLV-1 provirus in 60 ATL cases. Abortive genetic changes, including deletions, insertions, and nonsense mutations, were frequent in all viral genes except the HBZ gene, which is transcribed from the minus strand of the virus. G-to-A base substitutions were the most frequent mutations in ATL cells. The sequence context of G-to-A mutations was in accordance with the preferred target sequence of human APOBEC3G (hA3G). The target sequences of hA3G were less frequent in the plus strand of the HBZ coding region than in other coding regions of the HTLV-1 provirus. Nonsense mutations in viral genes including tax were also observed in proviruses from asymptomatic carriers, indicating that these mutations were generated during reverse transcription and prior to oncogenesis. The fact that hA3G targets the minus strand during reverse transcription explains why the HBZ gene is not susceptible to such nonsense mutations. HTLV-1-infected cells likely take advantage of hA3G to escape from the host immune system by losing expression of viral proteins.

Three-dimensional (3D) bioprinting, known as a promising technology for bioartificial organ manufacturing, has provided unprecedented versatility to manipulate cells and other biomaterials with precise control their locations in space. Over the last decade, a number of 3D bioprinting technologies have been explored. Natural polymers have played a central role in supporting the cellular and biomolecular activities before, during and after the 3D bioprinting processes. These polymers have been widely used as effective cell-loading hydrogels for homogeneous/heterogeneous tissue/organ formation, hierarchical vascular/neural/lymphatic network construction, as well as multiple biological/biochemial/physiological/biomedical/pathological functionality realization. This review aims to cover recent progress in natural polymers for bioartificial organ 3D bioprinting. It is structured as introducing the important properties of 3D printable natural polymers, successful models of 3D tissue/organ construction and typical technologies for bioartificial organ 3D bioprinting.

Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat antiOsteopontin (OPN) is a highly acidic glycoprotein that contains an adhesive arginine-glycine-aspartic acid sequence.1 OPN functions as a cell adhesion and migration molecule which can bind to a number of ligands including the ␣v␤3 integrin (vitronectin receptor), CD44, collagen type I, and fibronectin.1-3 A wide range of cell types including osteoclasts, some epithelia, macrophages, T cells, smooth muscle cells, and some tumors has been shown to express OPN in a constitutive or inducible fashion.2-9 The adhesive functions of OPN are thought to be involved in diverse biological activities such as bone absorption, tumor metastasis, and inhibition of renal stone formation. 2,9 -11 A functional role for OPN in monocyte infiltration at sites of inflammation has recently been established. OPN, which binds avidly to macrophages, induces prominent monocyte infiltration when injected subcutaneously in mice. 12 In addition, macrophage accumulation induced by intradermal injection of the chemoattractant N-formyl-met-leu-phe in rats is inhibited by administration of a neutralizing anti-OPN antibody. 13Macrophage infiltration is thought to play an important role in mediating renal injury in both immune and nonimmune forms of kidney disease.14 A clear association between up-regulation of OPN expression and macrophage infiltration has been described in a wide range of experimental models of glomerular and interstitial nephritis. [15][16][17][18][19][20][21][22] A functional role for OPN in promoting macrophage-mediated renal injury has recently been demonstrated in rat crescentic anti-glomerular basement

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

This study provides the first phenotypic and morphological evidence that glomerular epithelial-myofibroblast transdifferentiation participates in the formation and evolution of glomerular crescents.

BackgroundNeuroblastoma (NB) is the most common extracranial solid tumor in childhood. The present treatment including surgery, chemotherapy and radiation, which have only 40% long-term cure rates, and usually cause tumor recurrence. Thus, looking for new effective and less toxic therapies has important significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism.MethodsIn the present study, we used both XAV939 treatment and RNAi method to demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT method was used for determining the cell viability and the appropriate concerntration for follow-up assays. The colony formation assay, Annexin V staining and cell cycle analysis were used for detecting colony forming ability, cell apoptosis and the percentage of different cell cycle. The Western blot was used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/β-catenin) signaling pathway.ResultsThe results showed that TNKS1 inhibition decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1 inhibition may in part blocked Wnt/β-catenin signaling and reduced the expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1 inhibition decreased colony formation in vitro.ConclusionsThese findings suggested that TNKS1 may be a potential molecule target for the treatment of NB.