Cell-Based Therapy Approaches: The Hope for Incurable Diseases

Buzhor, Ella; Leshansky, Lucy; Blumenthal, Jacob B.; Barash, Hila; Warshawsky, David; Mazor, Yaron; Shtrichman, Ronit

doi:10.2217/rme.14.35

Cited by 145 publications

(108 citation statements)

References 181 publications

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“…Many neurological diseases and disorders lack true cures, making them attractive targets for cell therapies. In terms of pre-clinical work, it is anticipated that a Phase I clinical trial will be launched to evaluate the ability of human ESC-derived dopaminergic neurons to treat Parkinson's Disease in the near future [12]. Other promising targets for ESC-derived therapies include treating diabetes and heart disease [13,14].…”

Section: Pluripotent Stem Cells and Their Promise For Tissue Engineermentioning

confidence: 99%

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

Mohtaram¹,

Karamzadeh

Shafieyan³

et al. 2017

Electrospinning

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Tissue engineering, the process of combining bioactive scaffolds often with cells to produce replacements for damaged organs, represents an enormous market opportunity. This review critically evaluates the commercialization potential of electrospun scaffolds for applications in stem cell biology, including tissue engineering. First, it provides an overview of pluripotent stem cells (PSCs) and their defining properties, pluripotency and the ability to self-renew. These cells serve as an important tool for engineering tissues, including for clinical applications. Next, we review the technique of electrospinning and its promise for fabricating cell culture substrates and scaffolds for directing tissue formation from stem cells and compare these scaffolds to existing technologies, such as hydrogels. We address the associated market for electrospun scaffolds for PSCs and its potential for growth along with highlighting the importance of 3D cell culture substrates for PSCs by analyzing the net capital invested in this market and the associated growth rate. This review finishes by detailing the current state of commercializing electrospun scaffolds along with pathways for translating these scaffolds from research laboratories into successful start-up companies and the associated challenges with this process.

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Section: Pluripotent Stem Cells and Their Promise For Tissue Engineermentioning

confidence: 99%

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

Mohtaram¹,

Karamzadeh

Shafieyan³

et al. 2017

Electrospinning

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“…1- 4 Tracking of stem cells in pre-clinical models is a prerequisite to determine their safety and efficacy. [5][6][7] For this purpose, in addition to, and/or in combination with genetic reporters, nanoparticles are successfully used as contrast agents for cell labelling and tracking with various imaging modalities.…”

Section: Introductionmentioning

confidence: 99%

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

Ashraf

Taylor

Sharkey

et al. 2018

Preprint

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Nanoparticle contrast agents are useful tools to label stem cells and monitor the in vivo biodistribution of labeled cells in pre-clinical models of disease. In this context, understanding the in vivo fate of the particles after injection of labelled cells is important for their eventual clinical use as well as for the interpretation of imaging results. We examined how the formulation of superparamagnetic iron oxide nanoparticles (SPIONs) impacts the labelling efficiency, magnetic characteristics and fate of the particles by comparing individual SPIONs with polyelectrolyte multilayer capsules containing SPIONs. At low labelling concentration, encapsulated SPIONs served as an efficient labelling agent for stem cells. The bio-distribution after intra-cardiac injection of labelled cells was monitored longitudinally by MRI and as an endpoint by inductively coupled plasma-optical emission spectrometry. The results suggest that, after being released from labelled cells after cell death, both formulations of particles are initially stored in liver and spleen and are not completely cleared from these organs 2 weeks post-injection.

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“…Stem cell based therapies hold great promise for the future of regenerative medicine, and could potentially be used to treat a wide variety of diseases, from autoimmunity to neurodegeneration to cancer, as shown in the literature 3 . However, if the differentiation process of pluripotent cells is not perfect, or if random mutations occur during in vitro culture, transplanted cells could become cancerous 1 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of the nitroreductase/metronidazole suicide gene system as a safeguard for cell based therapies

Li¹

2017

JSST

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Cell-based therapies are promising treatment strategies for a variety of disorders ranging from cancer to spinal cord injuries. However, there is a risk of the transplanted cells becoming malignant. As a safeguard against this, suicide gene systems can be implemented so that transplanted cells can be eliminated if necessary by administering a pro-drug. Herpes simplex virus thymidine kinase (HSV-tk) paired with the pro-drug ganciclovir (GCV) is one of the most studied suicide gene systems. However, it can only kill cells that are actively dividing. Here we characterize another suicide gene system, nitroreductase (NTR) with its pro-drug metronidazole (MNZ), to investigate where in the cell cycle the killing occurs, hypothesizing that it could become an ideal candidate for eliminating transplanted cells irrespective of their proliferative status. Murine embryonic stem cells were transfected with vectors expressing either HSV-tk or NTR and treated with the corresponding pro-drug. Confocal imaging and FUCCI (fluorescent ubiquitination-based cell cycle indicator) were used to identify where in the cell cycle the drug was active . MNZ was found to kill both dividing and non-dividing cells whereas GCV killed only the dividing cells. These results suggest that the NTR system may be a valuable addition or complement to HSV-tk.Les thérapies cellulaires sont des stratégies promettantes en tant que traitements pour une variété de maladies. Celles-ci incluent le cancer et les traumatismes médullaires. Cependant, il y a un risque que les cellules implantées puissent devenir malignes. Afin de prévenir cela, des systèmes de gènes suicides peuvent être utilisés afin d'éliminer les cellules implantées si nécessaires par l'administration d'une prodrogue. La thymidine kinase, une enzyme trouvée chez les patients atteint du virus de l'herpès simplex (HSV-tk), utilisée en conjonction avec la prodrogue ganciclovir (GCV), est un des systèmes de gènes suicides les plus étudiés. Cependant, il peut seulement tuer les cellules qui se divisent activement. Ici, nous caractérisons un autre système de gènes suicidaires, nitroréductase (NTR) avec sa prodrogue metronidazole (MNZ), afin d'étudier à quel point dans le cycle cellulaire la tuerie se déroule. L'hypothèse est que ce système pourrait être un candidat idéal afin d'éliminer les cellules transplantées, peu importe leur statut prolifératif. Des cellules de souche embryonnaires murines ont été transfectées avec des vecteurs qui exprimaient soit HSV-tk ou NTR et traitées avec la prodrogue correspondante. La microscopie confocale et le système FUCCI (pour fluorescent ubiquitination-based cell cycle indicator) ont été utilisés afin d'identifier le point du cycle pendant lequel la drogue était active 2 . Il a été trouvé que MNZ tuait les cellules qui se divisaient et qui ne se divisaient pas, alors que GCV tuait uniquement les cellules qui se divisent. Ces résultats suggèrent que le système NTR pourrait être une addition ou un complément utile à HSV-tk.

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Cell-Based Therapy Approaches: The Hope for Incurable Diseases

Cited by 145 publications

References 181 publications

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

Characterization of the nitroreductase/metronidazole suicide gene system as a safeguard for cell based therapies

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