A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma

Mirani, Bahram; Pagan, Erik; Shojaei, Shahla; Duchscherer, Jade; Toyota, Brian; Ghavami, Saeid; Akbari, Mohsen

doi:10.1016/j.ejphar.2019.04.007

Cited by 45 publications

(37 citation statements)

References 60 publications

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“…Extensive genetic and cellular diversities render GBM difficult to treat and eradicate. In spite of various modalities of treatments, overall survival has only modestly increased over the last 30 years [3,8,33,34]. Immune cell therapy has emerged as a promising tool to tackle GBM [35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, GBM grows fast and can spread quickly [5][6][7]. Localization of the tumor in the brain tends to aggravate its very aggressive nature, as it is out of the reach of the immune system; at the same time, brain cells have limited capacity to repair themselves [1,8]. Furthermore, leakage of the tumor capillaries causes fluid accumulation around the tumor and contributes to the aforementioned increase in intracranial pressure [2,8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Localization of the tumor in the brain tends to aggravate its very aggressive nature, as it is out of the reach of the immune system; at the same time, brain cells have limited capacity to repair themselves [1,8]. Furthermore, leakage of the tumor capillaries causes fluid accumulation around the tumor and contributes to the aforementioned increase in intracranial pressure [2,8,9]. Current mainstay therapy for newly diagnosed GBM patients consists of a maximal resection within the safety limits; however, the tumor is usually infiltrative and complete resection is typically impossible, and resection must therefore be followed by radio-and chemotherapy [3,10].…”

Section: Introductionmentioning

confidence: 99%

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HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

Sharifzad

Mardpour

et al. 2020

IJMS

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Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein 70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intracranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2-treated NK cells as compared to those subjected to nontreated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2-treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

Sharifzad

Mardpour

et al. 2020

IJMS

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“…Three-dimensional (3D) printing is a promising technique for fabricating implantable hydrogels for various biomedical applications [24,[26][27][28][29]. These types of hydrogels have been reported in the literature as a potential scaffold for post-surgery applications in in vivo experiments [30,31].…”

Section: Implantable Hydrogelsmentioning

confidence: 99%

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Askari

Seyfoori

Amereh

et al. 2020

Gels

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Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

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Section: Introductionmentioning

confidence: 99%

HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

Sharifzad¹,

Mardpour²,

Mardpour³

et al. 2020

Preprint

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Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naï ve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models.In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site.Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells.Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 25 February 2020

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A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma

Cited by 45 publications

References 60 publications

HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

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