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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

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Abstract

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow–derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

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Acknowledgements

The authors would like to thank the Clinical Research Development Unit of Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, for their support and assistance with this research.

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Author notes

  1. Saeed Oraee-Yazdani, Ali-Reza Zali and Masoud Soleimanicontributed equally to this work.

Authors and Affiliations

  1. Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Saeed Oraee-Yazdani, Mohammadhosein Akhlaghpasand, Maryam Golmohammadi, Maryam Oraee-Yazdani & Ali-Reza Zali

  2. Stem Cell Technology Research Center, Tehran, Iran

    Gelareh Shokri

  3. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Fatemeh Rostami

  4. Laboratory for Stem Cell & Regenerative Medicine, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman

    Fatemeh Jamshidi-Adegani

  5. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran

    Ehsan Arefian

  6. Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran

    Maryam Hafizi

  7. Applied Cell Sciences and Hematology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Mina Soufi Zomorrod & Masoud Soleimani

Authors
  1. Saeed Oraee-Yazdani
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Contributions

S.O.Y., M.H.A.P., and M.G. prepared the original draft; S.O.Y., A.R.Z., and M.S. finalized all drafts and approved the final version of the manuscript; S.O.Y. and A.R.Z. conceptualized the study and provided supervision; S.O.Y., M.H.A.P., M.G., G.S., F.R., and F.J.A. were involved in conducting the trial; all other authors were involved in data gathering; all authors reviewed and revised the manuscript.

Corresponding authors

Correspondence to Saeed Oraee-Yazdani, Ali-Reza Zali or Masoud Soleimani.

Ethics declarations

Ethics Approval and Consent to Participate

This study was designed in line with the declaration of Helsinki and was approved by the Ethics committee in the Medical Research Committee of the Shahid Beheshti University of Medical Sciences; license number: IR.SBMU.REC.1396.224 and clinical trial registration number: IRCT20200502047277N2. All procedures were performed after written informed consent was obtained. Written consent included procedures of culture and analyses of biopsies from the tissue. Patients were fully aware of the experimental process of the treatment, unexpected outcomes, and possible or unforeseen adverse effects.

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Patients have consented to the submission of the present study to the journal.

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The authors declare no competing interests.

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Oraee-Yazdani, S., Akhlaghpasand, M., Shokri, G. et al. Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment. Mol Neurobiol 58, 4425–4436 (2021). https://doi.org/10.1007/s12035-021-02393-y

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