Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma
Mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, and anti-tumor and immunoregulatory properties. The limited passage and self-differentiation abilities of MSCs in vitro hinder preclinical studies on them. In this study, we focused on the...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2022/6430565 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562391022305280 |
|---|---|
| author | Yuxuan Zhang Jie Liu Yunzhao Mo Zetao Chen Taoliang Chen Yan Li Yaofeng Zheng Shaokang Deng Xiangdong Xu Huajian Chen Haoqi He Jiansheng Chen Tao Jin Xinlin Sun Yiquan Ke Jihui Wang |
| author_facet | Yuxuan Zhang Jie Liu Yunzhao Mo Zetao Chen Taoliang Chen Yan Li Yaofeng Zheng Shaokang Deng Xiangdong Xu Huajian Chen Haoqi He Jiansheng Chen Tao Jin Xinlin Sun Yiquan Ke Jihui Wang |
| author_sort | Yuxuan Zhang |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, and anti-tumor and immunoregulatory properties. The limited passage and self-differentiation abilities of MSCs in vitro hinder preclinical studies on them. In this study, we focused on the safety of immortalized mesenchymal stem cells (im-MSCs) and, for the first time, studied the feasibility of im-MSCs as candidates for the treatment of glioma. The im-MSCs were constructed by lentiviral transfection of genes. The proliferative capacity of im-MSCs and the proliferative phenotype of MSCs and MSCs co-cultured with glioma cells (U87) were measured using CCK-8 or EdU assays. After long-term culture, karyotyping of im-MSCs was conducted. The tumorigenicity of engineered MSCs was evaluated using soft agar cloning assays. Next, the engineered cells were injected into the brain of female BALB/c nude mice. Finally, the cell membranes of im-MSCs were labeled with DiO or DiR to detect their ability to be taken up by glioma cells and target in situ gliomas using the IVIS system. Engineered cells retained the immunophenotype of MSC; im-MSCs maintained the ability to differentiate into mesenchymal lineages in vitro; and im-MSCs showed stronger proliferative capacity than unengineered MSCs but without colony formation in soft agar, no tumorigenicity in the brain, and normal chromosomes. MSCs or im-MSCs co-cultured with U87 cells showed enhanced proliferation ability, but did not show malignant characteristics in vitro. Immortalized cells continued to express homing molecules. The cell membranes of im-MSCs were taken up by glioma cells and targeted in situ gliomas in vivo, suggesting that im-MSCs and their plasma membranes can be used as natural drug carriers for targeting gliomas, and providing a safe, adequate, quality-controlled, and continuous source for the treatment of gliomas based on whole-cell or cell membrane carriers. |
| format | Article |
| id | doaj-art-2df47761833c49e2864ba3ac08b35b68 |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-2df47761833c49e2864ba3ac08b35b682025-02-03T01:22:46ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/6430565Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of GliomaYuxuan Zhang0Jie Liu1Yunzhao Mo2Zetao Chen3Taoliang Chen4Yan Li5Yaofeng Zheng6Shaokang Deng7Xiangdong Xu8Huajian Chen9Haoqi He10Jiansheng Chen11Tao Jin12Xinlin Sun13Yiquan Ke14Jihui Wang15The National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyThe National Key Clinical SpecialtyMesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, and anti-tumor and immunoregulatory properties. The limited passage and self-differentiation abilities of MSCs in vitro hinder preclinical studies on them. In this study, we focused on the safety of immortalized mesenchymal stem cells (im-MSCs) and, for the first time, studied the feasibility of im-MSCs as candidates for the treatment of glioma. The im-MSCs were constructed by lentiviral transfection of genes. The proliferative capacity of im-MSCs and the proliferative phenotype of MSCs and MSCs co-cultured with glioma cells (U87) were measured using CCK-8 or EdU assays. After long-term culture, karyotyping of im-MSCs was conducted. The tumorigenicity of engineered MSCs was evaluated using soft agar cloning assays. Next, the engineered cells were injected into the brain of female BALB/c nude mice. Finally, the cell membranes of im-MSCs were labeled with DiO or DiR to detect their ability to be taken up by glioma cells and target in situ gliomas using the IVIS system. Engineered cells retained the immunophenotype of MSC; im-MSCs maintained the ability to differentiate into mesenchymal lineages in vitro; and im-MSCs showed stronger proliferative capacity than unengineered MSCs but without colony formation in soft agar, no tumorigenicity in the brain, and normal chromosomes. MSCs or im-MSCs co-cultured with U87 cells showed enhanced proliferation ability, but did not show malignant characteristics in vitro. Immortalized cells continued to express homing molecules. The cell membranes of im-MSCs were taken up by glioma cells and targeted in situ gliomas in vivo, suggesting that im-MSCs and their plasma membranes can be used as natural drug carriers for targeting gliomas, and providing a safe, adequate, quality-controlled, and continuous source for the treatment of gliomas based on whole-cell or cell membrane carriers.http://dx.doi.org/10.1155/2022/6430565 |
| spellingShingle | Yuxuan Zhang Jie Liu Yunzhao Mo Zetao Chen Taoliang Chen Yan Li Yaofeng Zheng Shaokang Deng Xiangdong Xu Huajian Chen Haoqi He Jiansheng Chen Tao Jin Xinlin Sun Yiquan Ke Jihui Wang Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma Stem Cells International |
| title | Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma |
| title_full | Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma |
| title_fullStr | Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma |
| title_full_unstemmed | Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma |
| title_short | Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma |
| title_sort | immortalized mesenchymal stem cells a safe cell source for cellular or cell membrane based treatment of glioma |
| url | http://dx.doi.org/10.1155/2022/6430565 |
| work_keys_str_mv | AT yuxuanzhang immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT jieliu immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT yunzhaomo immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT zetaochen immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT taoliangchen immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT yanli immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT yaofengzheng immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT shaokangdeng immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT xiangdongxu immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT huajianchen immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT haoqihe immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT jianshengchen immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT taojin immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT xinlinsun immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT yiquanke immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma AT jihuiwang immortalizedmesenchymalstemcellsasafecellsourceforcellularorcellmembranebasedtreatmentofglioma |