In vivo therapeutic applications of cell spheroids

Ong, Chin Siang; Zhou, Xun; Han, Joan C.; Huang, Chen Yu; Nashed, Andrew; Khatri, Shipra; Mattson, Gunnar; Fukunishi, Takuma; Zhang, Huaitao; Hibino, Narutoshi

doi:10.1016/j.biotechadv.2018.02.003

Cited by 64 publications

(46 citation statements)

References 88 publications

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“…In this study, human fibroblasts were selected as the cell source because of the ease of harvesting and maintenance in culture, which is important when considering clinical applications. Moreover, fibroblasts spheroids are necessary for building the 3D constructs, because the ECM produced by fibroblasts helps maintain their structure and the ECM molecules contained in the spheroids support nerve regeneration and provide a place for binding neurotropic factors or growth factors (Alba, Lacour, Raffoul, & diSumma, ; Ong et al, ). Furthermore, recent studies reported that fibroblasts play a role in helping to accumulate Schwann cells or directly converting into Schwann cells (Kitada, Murakami, Wakao, Li, & Dezawa, ; Parrinello, Napoli, Ribeiro, et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The Bio 3D conduits were fabricated by using a "Bio-3D printer (Regenova ® , Cyfuse, Tokyo, Japan)" to assemble the spheroids for constructing a tubular structure, as previously described (Itoh et al, 2015;Moldovan, Hibino, & Nakayama, 2017;Ong, Zhou, Han, et al, 2018;Takeoka, Matsumoto, Taniguchi, et al, 2019;Taniguchi et al, 2018;Yurie et al, 2017;Zhang et al, 2018). Briefly, spheroids were robotically picked out from the 96-well plate using a 25-gauge suction nozzle and inserted into a needle array unit according to a 3-dimensional computer-aided design that specified the shape of the tubular construct ( Figure 1b).…”

Section: Spheroid Generation and Fabrication Of Bio 3d Conduitsmentioning

confidence: 99%

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A scaffold‐free Bio 3D nerve conduit for repair of a 10‐mm peripheral nerve defect in the rats

et al. 2019

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Introduction A Bio 3D printed nerve conduit was reported to promote nerve regeneration in a 5 mm nerve gap model. The purpose of this study was to fabricate Bio 3D nerve conduits suitable for a 10 mm nerve gap and to evaluate their capacity for nerve regeneration in a rat sciatic nerve defect model. Materials and Methods Eighteen F344 rats with immune deficiency (9–10 weeks old; weight, 200–250 g) were divided into three groups: a Bio 3D nerve conduit group (Bio 3D, n = 6), a nerve graft group (NG, n = 6), and a silicon tube group (ST, n = 6). A 12‐mm Bio 3D nerve conduit or silicon tube was transplanted into the 10‐mm defect of the right sciatic nerve. In the nerve graft group, reverse autografting was performed with an excised 10‐mm nerve segment. Assessments were performed at 8 weeks after the surgery. Results In the region distal to the suture site, the number of myelinated axons in the Bio 3D group were significantly larger compared with the silicon group (2,548 vs. 950, p < .05). The myelinated axon diameter (MAD) and the myelin thickness (MT) of the regenerated axons in the Bio 3D group were significantly larger compared with those of the ST group (MAD: 3.09 vs. 2.36 μm; p < .01; MT: 0.59 vs. 0.40 μm, p < .01). Conclusions This study indicates that a Bio 3D nerve conduit can enhance peripheral nerve regeneration even in a 10 mm nerve defect model.

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Section: Discussionmentioning

confidence: 99%

Section: Spheroid Generation and Fabrication Of Bio 3d Conduitsmentioning

confidence: 99%

A scaffold‐free Bio 3D nerve conduit for repair of a 10‐mm peripheral nerve defect in the rats

et al. 2019

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“…With the intent to reduce the amount of data acquired, we next determined an appropriate image acquisition regime in the xyz dimensions ( Figure A; Supporting Information). We used this as a strategy to identify the widest cross‐section or equatorial (EQ) plane of individual 3D structures (Figure B), which can then be used for assessment of nanoparticle penetration to the center of the spheroid . An initial series of 70 z ‐planes with 0.5 µm spacing was acquired in a 10.4 mm 2 of the well area (≈ 30% of the total surface).…”

Section: Resultsmentioning

confidence: 99%

A High‐Throughput Automated Confocal Microscopy Platform for Quantitative Phenotyping of Nanoparticle Uptake and Transport in Spheroids

Cutrona

Simpson

2019

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There is a high demand for advanced, image‐based, automated high‐content screening (HCS) approaches to facilitate phenotypic screening in 3D cell culture models. A major challenge lies in retaining the resolution of fine cellular detail but at the same time imaging multicellular structures at a large scale. In this study, a confocal microscopy‐based HCS platform in optical multiwell plates that enables the quantitative morphological profiling of populations of nonuniform spheroids obtained from HT‐29 human colorectal cancer cells is described. This platform is then utilized to demonstrate a quantitative dissection of the penetration of synthetic nanoparticles (NP) in multicellular 3D spheroids at multiple levels of scale. A pilot RNA interference‐based screening validates this methodology and identifies a subset of RAB GTPases that regulate NP trafficking in these spheroids. This technology is suitable for high‐content phenotyping in 3D cell‐based screening, providing a framework for nanomedicine drug development as applied to translational oncology.

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“…8 In vitro therapeutic applications of cell spheroids: spheroid formation methods and organ systems for potential clinical applications. 94 Reprinted with permission from ref. 94.…”

Section: Biosensorsmentioning

confidence: 99%