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1
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Lahouty M, Soleymanzadeh A, Kazemi S, Saadati-Maleki H, Masoudi S, Ghasemi A, Kazemi T, Mehranfar S, Fadaee M. Cell-based immunotherapy in oesophageal cancer. J Drug Target 2025:1-11. [PMID: 40063049 DOI: 10.1080/1061186x.2025.2477077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/18/2025] [Accepted: 03/03/2025] [Indexed: 03/18/2025]
Abstract
Oesophageal cancer (EC) is among the most common illnesses globally, and its prognosis is unfavourable. Surgery, radiotherapy and chemotherapy are the primary therapy options for EC. Despite the occasional efficacy of these traditional treatment modalities, individuals with EC remain at a significant risk for local recurrence and metastasis. Consequently, innovative and efficacious medicines are required. In recent decades, clinical practice has effectively implemented cell therapy, which includes both stem cell and non-stem cell-based approaches, as an innovative tumour treatment, offering renewed hope to patients with oesophageal squamous cell carcinoma (ESCC). This paper examines the theoretical framework and contemporary advancements in cell treatment for individuals with EC. We further described current clinical studies and summarised essential data related to survival and safety assessments.
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Affiliation(s)
- Masoud Lahouty
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sama Kazemi
- Faculty of Medicine, Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Haniyeh Saadati-Maleki
- Faculty of Medicine, Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Sanaz Masoudi
- Faculty of Medicine, Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Arash Ghasemi
- Faculty of Medicine, Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Tohid Kazemi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sahar Mehranfar
- Department of Genetics and Immunology, Urmia University of Medical Sciences, Urmia, Iran
| | - Manouchehr Fadaee
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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2
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Araújo NM, Rubio IGS, Toneto NPA, Morale MG, Tamura RE. The use of adenoviral vectors in gene therapy and vaccine approaches. Genet Mol Biol 2022; 45:e20220079. [PMID: 36206378 PMCID: PMC9543183 DOI: 10.1590/1678-4685-gmb-2022-0079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 07/12/2022] [Indexed: 11/04/2022] Open
Abstract
Adenovirus was first identified in the 1950s and since then this pathogenic group
of viruses has been explored and transformed into a genetic transfer vehicle.
Modification or deletion of few genes are necessary to transform it into a
conditionally or non-replicative vector, creating a versatile tool capable of
transducing different tissues and inducing high levels of transgene expression.
In the early years of vector development, the application in monogenic diseases
faced several hurdles, including short-term gene expression and even a fatality.
On the other hand, an adenoviral delivery strategy for treatment of cancer was
the first approved gene therapy product. There is an increasing interest in
expressing transgenes with therapeutic potential targeting the cancer hallmarks,
inhibiting metastasis, inducing cancer cell death or modulating the immune
system to attack the tumor cells. Replicative adenovirus as vaccines may be even
older and date to a few years of its discovery, application of non-replicative
adenovirus for vaccination against different microorganisms has been
investigated, but only recently, it demonstrated its full potential being one of
the leading vaccination tools for COVID-19. This is not a new vector nor a new
technology, but the result of decades of careful and intense work in this
field.
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Affiliation(s)
- Natália Meneses Araújo
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil.
| | - Ileana Gabriela Sanchez Rubio
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil. ,Universidade Federal de São Paulo, Laboratório de Ciências
Moleculares da Tireóide, Diadema, SP, Brazil.
| | | | - Mirian Galliote Morale
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil. ,Universidade Federal de São Paulo, Laboratório de Ciências
Moleculares da Tireóide, Diadema, SP, Brazil.
| | - Rodrigo Esaki Tamura
- Universidade Federal de São Paulo, Laboratório de Biologia Molecular
do Câncer, São Paulo, SP, Brazil. ,Universidade Federal de São Paulo, Departamento de Ciências
Biológicas, Diadema, SP, Brazil.
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3
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Xiang Z, Hua M, Hao Z, Biao H, Zhu C, Zhai G, Wu J. The Roles of Mesenchymal Stem Cells in Gastrointestinal Cancers. Front Immunol 2022; 13:844001. [PMID: 35281017 PMCID: PMC8907448 DOI: 10.3389/fimmu.2022.844001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/03/2022] [Indexed: 12/19/2022] Open
Abstract
Mesenchymal stem cells (MSCs) were reported to have strong immunomodulatory ability, and inhibit the proliferation of T cells and their immune response through cell-to-cell interactions and the generation of cytokines. With high differentiation potential and self-renewal ability, MSCs are considered to function in alleviating inflammatory responses, promoting tissue regeneration and inhibiting tissue fibrosis formation. As the most common malignancies, gastrointestinal (GI) cancers have high incidence and mortality. The accurate diagnosis, exact prognosis and treatment of GI cancers have always been a hot topic. Therefore, the potential applications of MSCs in terms of GI cancers are receiving more and more attention. Recently, there is increasing evidence that MSCs may serve as a key point in the growth, metastasis, inhibition, treatment and prognosis of GI cancers. In this review, we summarized the roles of MSCs in GI cancers, mainly focusing on esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), colorectal cancer (CRC) and pancreatic cancer. Besides, we proposed MSCs as potential targets and treatment strategies for the effective treatment of GI cancers, which may provide better guidance for the clinical treatment of GI cancers.
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Affiliation(s)
- Ze Xiang
- School of Medicine, Zhejiang University, Hangzhou, China
| | - Menglu Hua
- School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhou Hao
- Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Huang Biao
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Chaojie Zhu
- School of Medicine, Zhejiang University, Hangzhou, China
| | - Guanghua Zhai
- Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Jian Wu
- Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
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4
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Vicinanza C, Lombardi E, Da Ros F, Marangon M, Durante C, Mazzucato M, Agostini F. Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications. World J Stem Cells 2022; 14:54-75. [PMID: 35126828 PMCID: PMC8788179 DOI: 10.4252/wjsc.v14.i1.54] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/06/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem stromal cells (MSC) are characterized by the intriguing capacity to home toward cancer cells after systemic administration. Thus, MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors. In cancer patients, MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited. Indeed, the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth. Moreover, induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy. Ex vivo cell modifications are, thus, required to improve anti-cancer properties of MSC. MSC based cellular therapy products must be handled in compliance with good manufacturing practice (GMP) guidelines. In the present review we include MSC-improving manipulation approaches that, even though actually tested at preclinical level, could be compatible with GMP guidelines. In particular, we describe possible approaches to improve MSC homing on cancer, including genetic engineering, membrane modification and cytokine priming. Similarly, we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods. In conclusion, we suggest that, to configure MSC as a powerful weapon against cancer, combinations of clinical grade compatible modification protocols that are currently selected, should be introduced in the final product. Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.
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Affiliation(s)
- Carla Vicinanza
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Elisabetta Lombardi
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Da Ros
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Miriam Marangon
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Cristina Durante
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Mario Mazzucato
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Agostini
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
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5
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Liu H, Deng S, Han L, Ren Y, Gu J, He L, Liu T, Yuan ZX. Mesenchymal stem cells, exosomes and exosome-mimics as smart drug carriers for targeted cancer therapy. Colloids Surf B Biointerfaces 2021; 209:112163. [PMID: 34736220 DOI: 10.1016/j.colsurfb.2021.112163] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 10/10/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022]
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity to differentiate into several cell types under appropriate conditions. They also possess remarkable antitumor features that make them a novel choice to treat cancers. Accumulating evidence suggest that the MSCs-derived extracellular vesicles, known as exosomes, play an essential role in the therapeutic effects of MSCs mainly by carrying biologically active factors. However, limitations such as low yield of exosomes and difficulty in isolation and purification hinder their clinical applications. To overcome these issues, research on development of exosome-mimics has attracted great attention. This systematic review represents, to the best of our knowledge, the first thorough evaluations of the innate antineoplastic features of MSCs-derived exosomes or exosome-mimics, the methods of drug loading, application as drug delivery system and their impacts on targeted cancer therapy. Importantly, we dissect the commonalities and differences as well as address the shortcomings of work accumulated over the last two decades and discuss how this information can serve as a guide map for optimal experimental design implementation ultimately aiding the effective transition into clinical trials.
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Affiliation(s)
- Hongmei Liu
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China
| | - Shichen Deng
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, Sichuan, China
| | - Lu Han
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China
| | - Yan Ren
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China
| | - Jian Gu
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China
| | - Lili He
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China.
| | - Tianqing Liu
- NICM Health Research Institute, Western Sydney University, Westmead, Australia.
| | - Zhi-Xiang Yuan
- College of Pharmacy, Southwest Minzu University, Chengdu 610041, China.
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6
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Razeghian E, Margiana R, Chupradit S, Bokov DO, Abdelbasset WK, Marofi F, Shariatzadeh S, Tosan F, Jarahian M. Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy. Front Med (Lausanne) 2021; 8:721174. [PMID: 34513882 PMCID: PMC8430327 DOI: 10.3389/fmed.2021.721174] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/30/2021] [Indexed: 12/22/2022] Open
Abstract
Pro-inflammatory cytokines can effectively be used for tumor immunotherapy, affecting every step of the tumor immunity cycle. Thereby, they can restore antigen priming, improve the effector immune cell frequencies in the tumor microenvironment (TME), and eventually strengthen their cytolytic function. A renewed interest in the anticancer competencies of cytokines has resulted in a substantial promotion in the number of trials to address the safety and efficacy of cytokine-based therapeutic options. However, low response rate along with the high toxicity associated with high-dose cytokine for reaching desired therapeutic outcomes negatively affect their clinical utility. Recently, mesenchymal stem/stromal cells (MSCs) due to their pronounced tropism to tumors and also lower immunogenicity have become a promising vehicle for cytokine delivery for human malignancies. MSC-based delivery of the cytokine can lead to the more effective immune cell-induced antitumor response and provide sustained release of target cytokines, as widely evidenced in a myriad of xenograft models. In the current review, we offer a summary of the novel trends in cytokine immunotherapy using MSCs as a potent and encouraging carrier for antitumor cytokines, focusing on the last two decades' animal reports.
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Affiliation(s)
- Ehsan Razeghian
- Human Genetics Division, Medical Biotechnology Department, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Ria Margiana
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Cipto Mangunkusumo Hospital, The National Referral Hospital, Central Jakarta, Indonesia
- Master's Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Dmitry O. Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia
- Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow, Russia
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Siavash Shariatzadeh
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Foad Tosan
- Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
| | - Mostafa Jarahian
- Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, Heidelberg, Germany
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7
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Razeghian E, Suksatan W, Sulaiman Rahman H, Bokov DO, Abdelbasset WK, Hassanzadeh A, Marofi F, Yazdanifar M, Jarahian M. Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges. Front Immunol 2021; 12:699746. [PMID: 34489946 PMCID: PMC8417882 DOI: 10.3389/fimmu.2021.699746] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 08/05/2021] [Indexed: 01/04/2023] Open
Abstract
The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.
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Affiliation(s)
- Ehsan Razeghian
- Human Genetics Division, Medical Biotechnology Department, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Heshu Sulaiman Rahman
- Department of Physiology, College of Medicine, University of Suleimanyah, Suleimanyah, Iraq
- Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Iraq
| | - Dmitry O. Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia
- Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow, Russia
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Ali Hassanzadeh
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahboubeh Yazdanifar
- Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States
| | - Mostafa Jarahian
- Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, Heidelberg, Germany
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Hassanzadeh A, Altajer AH, Rahman HS, Saleh MM, Bokov DO, Abdelbasset WK, Marofi F, Zamani M, Yaghoubi Y, Yazdanifar M, Pathak Y, Chartrand MS, Jarahian M. Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy. Front Cell Dev Biol 2021; 9:686453. [PMID: 34322483 PMCID: PMC8311597 DOI: 10.3389/fcell.2021.686453] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/10/2021] [Indexed: 12/17/2022] Open
Abstract
Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.
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Affiliation(s)
- Ali Hassanzadeh
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Heshu Sulaiman Rahman
- College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq
- Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaymaniyah, Iraq
| | - Marwan Mahmood Saleh
- Department of Biophysics, College of Applied Sciences, University of Anbar, Ramadi, Iraq
| | - Dmitry O. Bokov
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Zamani
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Yoda Yaghoubi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahboubeh Yazdanifar
- Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States
| | - Yashwant Pathak
- Professor and Associate Dean for Faculty Affairs, Taneja College of Pharmacy, University of South Florida, Tampa, FL, United States
- Adjunct Professor, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
| | | | - Mostafa Jarahian
- German Cancer Research Center, Toxicology and Chemotherapy Unit (G401), Heidelberg, Germany
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9
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Salmasi Z, Hashemi M, Mahdipour E, Nourani H, Abnous K, Ramezani M. Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo. Biotechnol Prog 2020; 36:e3025. [PMID: 32410328 DOI: 10.1002/btpr.3025] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 05/08/2020] [Accepted: 05/11/2020] [Indexed: 12/29/2022]
Abstract
Cell-based delivery system is a promising strategy to protect therapeutic agents from the immune system and provide targeted delivery. Mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in cell-based gene therapy due to their unique features including tumor-tropic property and migratory ability. However, gene transfer into MSCs is limited due to low efficiency and cytotoxicity of carriers. In this study, we designed a novel delivery system based on polyethylenimine (PEI25 ) to improve these features of carrier and transfect plasmid encoding TRAIL to MSCs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand of TNF family with selective effect on cancerous cells. Then, death induction and migration ability of TRAIL-expressing MSCs was studied in melanoma cells. The effect of engineered-MSCs as an antitumor vehicle was also investigated in mice bearing melanoma cells. Our findings indicated that heterocyclic amine derivative of PEI25 showed significant improvement in MSCs viability determined by MTT assay and gene expression using fluorescent microscopy, flow cytometry, and Western blot analysis. We observed that engineered-MSCs could migrate toward and induce cell death in B16F0 cells in vitro. The single administration of TRAIL-expressing MSCs could delay tumor appearance and efficiently reduce tumor weights. Hematoxylin and eosin staining of tumor sections revealed extensive neoplastic cells necrosis. Furthermore, engineered-MSCs could migrate and localize to tumors sites within 5 days. Our results indicated that MSCs engineered by modified-PEI/TRAIL complexes could be considered as a promising cellular vehicle for targeted tumor suppression.
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Affiliation(s)
- Zahra Salmasi
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Hashemi
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elahe Mahdipour
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Nourani
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Khalil Abnous
- Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ramezani
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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10
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Gao Y, Jin SZ. Strategies for treating oesophageal diseases with stem cells. World J Stem Cells 2020; 12:488-499. [PMID: 32742566 PMCID: PMC7360987 DOI: 10.4252/wjsc.v12.i6.488] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 05/02/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
There is a wide range of oesophageal diseases, the most general of which are inflammation, injury and tumours, and treatment methods are constantly being developed and updated. With an increasingly comprehensive understanding of stem cells and their characteristics of multilineage differentiation, self-renewal and homing as well as the combination of stem cells with regenerative medicine, tissue engineering and gene therapy, stem cells are playing an important role in the treatment of a variety of diseases. Mesenchymal stem cells have many advantages and are most commonly applied; however, most of these applications have been in experimental studies, with few related clinical trials for comparison. Therefore, the methods, positive significance and limitations of stem cells in the treatment of oesophageal diseases remain incompletely understood. Thus, the purpose of this paper is to review the current literature and summarize the efficacy of stem cells in the treatment of oesophageal diseases, including oesophageal ulceration, acute radiation-induced oesophageal injury, corrosive oesophageal injury, oesophageal stricture formation after endoscopic submucosal dissection and oesophageal reconstruction, as well as gene therapy for oesophageal cancer.
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Affiliation(s)
- Yang Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shi-Zhu Jin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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11
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LI A, ZHANG T, GAO J. [Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49:20-34. [PMID: 32621413 PMCID: PMC8800717 DOI: 10.3785/j.issn.1008-9292.2020.02.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 01/15/2020] [Indexed: 06/11/2023]
Abstract
Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
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Chulpanova DS, Kitaeva KV, Tazetdinova LG, James V, Rizvanov AA, Solovyeva VV. Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment. Front Pharmacol 2018; 9:259. [PMID: 29615915 PMCID: PMC5869248 DOI: 10.3389/fphar.2018.00259] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 03/08/2018] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs), which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.
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Affiliation(s)
- Daria S Chulpanova
- OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
| | - Kristina V Kitaeva
- OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
| | - Leysan G Tazetdinova
- OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
| | - Victoria James
- School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom
| | - Albert A Rizvanov
- OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
| | - Valeriya V Solovyeva
- OpenLab Gene and Cell Technologies, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
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Abstract
Mesenchymal stem cells (MSCs) have the capacity of multipotent differentiation and the property of immunomodulation. MSCs have been widely used in digestive system disease research because of their advantageous characteristics such as homing to areas of inflammation or tumour tissue, anti-inflammation, high plasticity, absence of immunologic rejection, being easy to be isolated, and being convenient for the expression of exogenous genes. In this article, we will review the application of mesenchymal stem cells in digestive system diseases including caustic esophagus injury, reflux esophagitis, gastric ulcer, radioactive intestinal injury, severe acute pancreatitis, inflammatory bowel disease, nonalcoholic steatohepatitis, acute liver failure, hepatic fibrosis, autoimmune liver diseases, liver cirrhosis, esophageal cancer, gastric cancer, colon cancer, liver cancer, and pancreatic cancer.
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