Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment

Oraee‐Yazdani, Saeed; Akhlaghpasand, Mohammadhosein; Shokri, Gelareh; Rostami, Fatemeh; Golmohammadi, Maryam; Jamshidi-Adegani, Fatemeh; Arefian, Ehsan; Hafizi, Maryam; Zomorrod, Mina Soufi; Oraee-Yazdani, Maryam; Zali, Alireza; Soleimani, Masoud

doi:10.1007/s12035-021-02393-y

Cited by 12 publications

(14 citation statements)

References 36 publications

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“…The patient was discharged a day after the procedure. Utilizing the protocol discussed in our previous study ( 8 ), samples went through a density gradient centrifugation by Ficol (density 1.077 g.L −1 , Sigma) at a ratio of 1:3. Samples were then centrifuged, and their mononuclear cell layer was recovered from the gradient interface.…”

Section: Case Presentationmentioning

confidence: 99%

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma

et al. 2023

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IntroductionThe prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects.Case presentationA 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days).ConclusionThe gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal).Trial registrationIRCT20200502047277N2. Registered 10 May 2020—Retrospectively registered, https://eng.irct.ir/trial/48110.

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Section: Case Presentationmentioning

confidence: 99%

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma

et al. 2023

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“…MSCs has attracted attention as promising drug carrier for the treatment of brain diseases. For instance, the use of MSCs as a vehicle for targeted gene therapy to the tumor is a novel therapeutic technique [ 32 ]. Studies have demonstrated the ability and efficiency of these cells in transferring genes to some tumors such as GBM, breast cancer, and small cell non-cell lung cancer.…”

Section: Mesenchymal Stromal/stem Cells (Mscs)mentioning

confidence: 99%

“…Due to MSCs strong regenerative activity, immunosuppressive, and immunomodulatory [ 33 , 34 ]. It seems that applied bone marrow MSC transplantation containing herpes simplex virus thymidine kinase (HSV-TK) gene in combination with prodrug ganciclovir (GCV) would be safe and feasible in the treatment of patients with GBM [ 32 ].…”

Section: Mesenchymal Stromal/stem Cells (Mscs)mentioning

confidence: 99%

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy in the brain tumors

et al. 2022

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Brain tumors are one of the most mortal cancers, leading to many deaths among kids and adults. Surgery, chemotherapy, and radiotherapy are available options for brain tumor treatment. However, these methods are not able to eradicate cancer cells. The blood–brain barrier (BBB) is one of the most important barriers to treat brain tumors that prevents adequate drug delivery to brain tissue. The connection between different brain parts is heterogeneous and causes many challenges in treatment. Mesenchymal stem cells (MSCs) migrate to brain tumor cells and have anti-tumor effects by delivering cytotoxic compounds. They contain very high regenerative properties, as well as support the immune system. MSCs-based therapy involves cell replacement and releases various vesicles, including exosomes. Exosomes receive more attention due to their excellent stability, less immunogenicity and toxicity compare to cells. Exosomes derived from MSCs can develop a powerful therapeutic strategy for different diseases and be a hopeful candidate for cell-based and cell-free regenerative medicine. These nanoparticles contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. Many studies show that each microRNA can prevent angiogenesis, migration, and metastasis in glioblastoma. These exosomes can—act as a suitable nanoparticle carrier for therapeutic applications of brain tumors by passing through the BBB. In this review, we discuss potential applications of MSC and their produced exosomes in the treatment of brain tumors.

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“…In addition, it is a new field that could be used in future for producing a more effective method for glioblastoma immunotherapy benefiting from both viral effects and nanomedicine without concerning the contamination resulted from virus infection. Recently, the herpes simplex virus type I thymidine kinase (HSV-tk) gene was delivered via different types of nanocarriers into the glioma cancer cells to increase the effectiveness of chemotherapy [ 225 , 226 ]. Although these studies were about the combination of gene therapy and chemotherapy, they could be considered as a preface for future investigations on the delivery of virus compounds with nanomaterials.…”

Section: Gbm–immunotherapy–bioengineeringmentioning

confidence: 99%

Immunology Meets Bioengineering: Improving the Effectiveness of Glioblastoma Immunotherapy

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Behrooz

Ghaemi

et al. 2022

Cancers

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Glioblastoma (GBM) therapy has seen little change over the past two decades. Surgical excision followed by radiation and chemotherapy is the current gold standard treatment. Immunotherapy techniques have recently transformed many cancer treatments, and GBM is now at the forefront of immunotherapy research. GBM immunotherapy prospects are reviewed here, with an emphasis on immune checkpoint inhibitors and oncolytic viruses. Various forms of nanomaterials to enhance immunotherapy effectiveness are also discussed. For GBM treatment and immunotherapy, we outline the specific properties of nanomaterials. In addition, we provide a short overview of several 3D (bio)printing techniques and their applications in stimulating the GBM microenvironment. Lastly, the susceptibility of GBM cancer cells to the various immunotherapy methods will be addressed.

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Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment

Cited by 12 publications

References 36 publications

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma

Case report: Stem cell-based suicide gene therapy mediated by the herpes simplex virus thymidine kinase gene reduces tumor progression in multifocal glioblastoma

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy in the brain tumors

Immunology Meets Bioengineering: Improving the Effectiveness of Glioblastoma Immunotherapy

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