Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies

Bhere, Deepak; Khajuria, Rajiv K.; Hendriks, William T.; Bandyopadhyay, Antara; Bagcı-Önder, Tugba; Shah, Khalid

doi:10.1002/stem.2805

Cited by 7 publications

(3 citation statements)

References 66 publications

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“…Methimazole can be used to promote the NSCs as therapeutic delivery vehicle to reach GBM by allowing it to cross-olfactory epithelium for intranasal delivery [ 92 ]. In a study, pluripotent stem cell (iPSC)-derived therapeutic NSCs (ipNSC) by using either unmodified or gene-modified somatic cells were engineered to express S-TRAIL and HSV-TK have antitumor impact when encapsulated in synthetic-extracellular matrix (sECM) and transplanted mouse of resected GBMs [ 93 ]. In a study, canine-induced NSCs (iNSCs) were engineered to deliver TNFα-related apoptosis-inducing ligand (TRAIL) and thymidine kinase (TK) which migrated to human tumor cells, to inhibit tumor growth [ 94 ].…”

Section: Neural Stem Cell-based Deliverymentioning

confidence: 99%

Systems Medicine for Precise Targeting of Glioblastoma

Zeng¹,

Zeng

2023

Mol Biotechnol

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Glioblastoma (GBM) is a malignant cancer that is fatal even after standard therapy and the effects of current available therapeutics are not promising due its complex and evolving epigenetic and genetic profile. The mysteries that lead to GBM intratumoral heterogeneity and subtype transitions are not entirely clear. Systems medicine is an approach to view the patient in a whole picture integrating systems biology and synthetic biology along with computational techniques. Since the GBM oncogenesis involves genetic mutations, various therapies including gene therapeutics based on CRISPR-Cas technique, MicroRNAs, and implanted synthetic cells endowed with synthetic circuits against GBM with neural stem cells and mesenchymal stem cells acting as potential vehicles carrying therapeutics via the intranasal route, avoiding the risks of invasive methods in order to reach the GBM cells in the brain are discussed and proposed in this review. Systems medicine approach is a rather novel strategy, and since the GBM of a patient is complex and unique, thus to devise an individualized treatment strategy to tailor personalized multimodal treatments for the individual patient taking into account the phenotype of the GBM, the unique body health profile of the patient and individual responses according to the systems medicine concept might show potential to achieve optimum effects.

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Section: Neural Stem Cell-based Deliverymentioning

confidence: 99%

Systems Medicine for Precise Targeting of Glioblastoma

Zeng¹,

Zeng

2023

Mol Biotechnol

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“…Immortalized human fetal NSC (hNSC) line, hNSC100, was provided by A. Martínez-Serrano, Autonomous University of Madrid. Mouse iPSC-NSC was generated from mouse embryonic fibroblasts as previously described ( 60 ).…”

Section: Methodsmentioning

confidence: 99%

Anti-EGFR VHH-armed death receptor ligand–engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers

et al. 2021

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Basal-like breast cancer (BLBC) shows brain metastatic (BM) capability and overexpresses EGFR and death-receptors 4/5 (DR4/5); however, the anatomical location of BM prohibits efficient drug-delivery to these targetable markers. In this study, we developed BLBC-BM mouse models featuring different patterns of BMs and explored the versatility of estem cell (SC)–mediated bi-functional EGFR and DR4/5-targeted treatment in these models. Most BLBC lines demonstrated a high sensitivity to EGFR and DR4/5 bi-targeting therapeutic protein, EVDRL [anti-EGFR VHH (EV) fused to DR ligand (DRL)]. Functional analyses using inhibitors and CRISPR-Cas9 knockouts revealed that the EV domain facilitated in augmenting DR4/5-DRL binding and enhancing DRL-induced apoptosis. EVDRL secreting stem cells alleviated tumor-burden and significantly increased survival in mouse models of residual-tumor after macrometastasis resection, perivascular niche micrometastasis, and leptomeningeal metastasis. This study reports mechanism based simultaneous targeting of EGFR and DR4/5 in BLBC and defines a new treatment paradigm for treatment of BM.

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“…The HSV-TK/GCV suicide-gene system was further demonstrated recently using human iPSC-derived NSCs and it showed considerable therapeutic potential for the treatment of GB [ 126 ]. Interestingly, in another study by Bhere et al iPSC-derived NSCs were engineered to secrete both TRAIL and HSV-TK and a profound antitumor efficacy was demonstrated [ 145 ] ( Figure 3 ).…”

Section: Cell Therapy For Glioblastomamentioning

confidence: 99%

Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies

Attia

Mashal

Pemminati

et al. 2021

Cells

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Glioblastoma (GB), an aggressive primary tumor of the central nervous system, represents about 60% of all adult primary brain tumors. It is notorious for its extremely low (~5%) 5-year survival rate which signals the unsatisfactory results of the standard protocol for GB therapy. This issue has become, over time, the impetus for the discipline of bringing novel therapeutics to the surface and challenging them so they can be improved. The cell-based approach in treating GB found its way to clinical trials thanks to a marvelous number of preclinical studies that probed various types of cells aiming to combat GB and increase the survival rate. In this review, we aimed to summarize and discuss the up-to-date preclinical studies that utilized stem cells or immune cells to treat GB. Likewise, we tried to summarize the most recent clinical trials using both cell categories to treat or prevent recurrence of GB in patients. As with any other therapeutics, cell-based therapy in GB is still hampered by many drawbacks. Therefore, we highlighted several novel techniques, such as the use of biomaterials, scaffolds, nanoparticles, or cells in the 3D context that may depict a promising future when combined with the cell-based approach.

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Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies

Cited by 7 publications

References 66 publications

Systems Medicine for Precise Targeting of Glioblastoma

Systems Medicine for Precise Targeting of Glioblastoma

Anti-EGFR VHH-armed death receptor ligand–engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers

Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies

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