Three-dimensional cell culturing by magnetic levitation

Haisler, William L.; Timm, David M.; Gage, Jacob A.; Tseng, Hubert; Killian, T. C.; Souza, Glauco R.

doi:10.1038/nprot.2013.125

Cited by 238 publications

(242 citation statements)

References 31 publications

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“…In our unique approach, magnetic beads were used to create 3-D cell spheroids of different human GBM cells lines 36 . These tumor spheroids were then suspended adjacent to fibrin-encapsulated SCs releasing the pro-apoptotic agent TRAIL.…”

Section: Discussionmentioning

confidence: 99%

Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer

et al. 2016

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Tumor-homing cytotoxic stem cell (SC) therapy is a promising new approach for treating the incurable brain cancer glioblastoma (GBM). However, problems of retaining cytotoxic SCs within the post-surgical GBM resection cavity are likely to significantly limit the clinical utility of this strategy. Here, we describe a new fibrin-based transplant approach capable of increasing cytotoxic SC retention and persistence within the resection cavity, yet remaining permissive to tumoritropic migration. This fibrin-based transplant can effectively treat both solid and post-surgical human GBM in mice. Using our murine model of image-guided model of GBM resection, we discovered that suspending human mesenchymal stem cells (hMSCS) in a fibrin matrix increased initial retention in the surgical resection cavity 2-fold and prolonged persistence in the cavity 3-fold compared to conventional delivery strategies. Time-lapse motion analysis revealed that cytotoxic hMSCs in the fibrin matrix remain tumoritropic, rapidly migrating from the fibrin matrix to co-localize with cultured human GBM cells. We encapsulated hMSCs releasing the cytotoxic agent TRAIL (hMSC-sTR) in fibrin, and found hMSC-sTR/fibrin therapy reduced the viability of multiple 3-D human GBM spheroids and regressed established human GBM xenografts 3-fold in 11 days. Mimicking clinical therapy of surgically resected GBM, intra-cavity seeding of therapeutic hMSC-sTR encapsulated in fibrin reduced post-surgical GBM volumes 6-fold, increased time to recurrence 4-fold, and prolonged median survival from 15 to 36 days compared to control-treated animals. Fibrin-based SC therapy could represent a clinically compatible, viable treatment to suppress recurrence of post-surgical GBM and other lethal cancer types.

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Section: Discussionmentioning

confidence: 99%

Fibrin matrices enhance the transplant and efficacy of cytotoxic stem cell therapy for post-surgical cancer

et al. 2016

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“…Another successful example is the magnetic nanobeads-mediated spheroid formation [41][42][43][44][45][46][47][48][49] . This method (also known as 'magnetic levitation' when the cells are collected on top of the fluid in a tissue culture well rather than on its bottom 41 ), is extremely versatile.…”

Section: Cell Spheroids As Building Blocks For Bioprintingmentioning

confidence: 99%

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

Moldovan

Hibino

Nakayama

2017

Tissue Engineering Part B: Reviews

252

204

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Abstract.Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live, de novo created bio-similar constructs. However, after more than a decade of incubation and many proofs-of-concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those which followed, were modified versions of the 3D printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, micro-extrusion or laser-assisted), this approach is material-('scaffold'-) dependent and energy-intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler, scaffoldfree bio-assembling methods. A substantial body of evidence has accumulated indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely 'print' spheroids has not been available until the invention of the microneedles-based ('Kenzan') spheroid assembling, and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel micro-needles ("kenzans') as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bio-engineering of tissues and organs.

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“…In this study, we report the facile fabrication method of liposomes with open lipid bilayer holes [hereafter referred to as partially uncapped liposomes (UCLs)] using highly dense and superparamagnetic Fe 3 O 4 nanoparticles and a magnetic impeller with a tailor-made magnet. We hypothesized that under magnetic shear stress, the Fe 3 O 4 nanoparticles [10] dispersed in the liposome would apply stress to a specific position of the lipid membrane via the strong magnetic field and the magnetic shear stress, which would consequently squeeze to form open lipid bilayer holes (Fig. 1a).…”

Section: Page 4 Of 20mentioning

confidence: 99%