Dataset Information

Polymeric Biomaterial Scaffolds for Tumoricidal Stem Cell Glioblastoma Therapy.

ABSTRACT: Glioblastoma (GBM) is the most common primary brain tumor and has a poor prognosis; as such, there is an urgent need to develop innovative new therapies. Tumoricidal stem cells are an emerging therapy that has the potential to combat limitations of traditional local and systemic chemotherapeutic strategies for GBM by providing a source for high, sustained concentrations of tumoricidal agents locally to the tumor. One major roadblock for tumoricidal stem cell therapy is that the persistence of tumoricidal stem cells injected as a cell suspension into the GBM surgical resection cavity is limited. Polymeric biomaterial scaffolds have been utilized to enhance the delivery of tumoricidal stem cells in the surgical resection cavity and extend their persistence in the brain, ultimately increasing their therapeutic efficacy against GBM. In this review, we examine three main scaffold categories explored for tumoricidal stem cell therapy: microcapsules, hydrogels, and electrospun scaffolds. Furthermore, considering the significant impact of surgery on the brain and recurrent GBM, we survey a brief history of orthotopic models of GBM surgical resection.

SUBMITTER: Moore KM

PROVIDER: S-EPMC10373914 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polymeric Biomaterial Scaffolds for Tumoricidal Stem Cell Glioblastoma Therapy.

Moore Kathryn M KM Murthy Ananya B AB Graham-Gurysh Elizabeth G EG Hingtgen Shawn D SD Bachelder Eric M EM Ainslie Kristy M KM

ACS biomaterials science & engineering 20200624 7

Glioblastoma (GBM) is the most common primary brain tumor and has a poor prognosis; as such, there is an urgent need to develop innovative new therapies. Tumoricidal stem cells are an emerging therapy that has the potential to combat limitations of traditional local and systemic chemotherapeutic strategies for GBM by providing a source for high, sustained concentrations of tumoricidal agents locally to the tumor. One major roadblock for tumoricidal stem cell therapy is that the persistence of tu ...[more]

PMID: 33463324

Similar Datasets

Project description:Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3 days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8 days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both in vitro and in vivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCstk) and transplanted the therapeutic cells in the post-operative cavity of mice bearing resected orthotopic patient-derived GBM xenografts. Following administration of the prodrug ganciclovir, residual tumor volumes in mice receiving GEM/tNSCs were reduced by 10-fold at day 35, and median survival was extended from 31 to 46 days. Taken together, these data begin to define design parameters for effective scaffold/tNSC composites and suggest a new approach to maximizing the efficacy of tNSC therapy in human patient trials.

Project description:Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an "ailment not to be treated" into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope that a cure for SCI was on the horizon. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. However, recent advances in SCI research have greatly increased our understanding of the fundamental processes underlying SCI and fostered increasing optimism that these multiple treatment strategies are finally coming together to bring about a new era in which we will be able to propose encouraging therapies that will lead to appreciable improvements in SCI patients. In this review, we outline the pathophysiology of SCI that makes the spinal cord refractory to regeneration and discuss the research that has been done with cell replacement and biomaterial implantation strategies, both by itself and as a combined treatment. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI.

Project description:Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell-material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of "Spinal cord injury" and ["Biomaterial", or "Scaffold"] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds.

Dataset Information

Polymeric Biomaterial Scaffolds for Tumoricidal Stem Cell Glioblastoma Therapy.

Publications

Polymeric Biomaterial Scaffolds for Tumoricidal Stem Cell Glioblastoma Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets