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A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer
Published on: December 26, 2016
Both human and mouse mesenchymal stem cells promote breast cancer metastasis
Stella Maris Albarenque1, Ralf Michael Zwacka, Andrea Mohr
1National University of Ireland, Galway, National Centre for Biomedical Engineering Science, Molecular Therapeutics Group, Galway, Ireland.
Abstract:
Cell therapy has the potential to offer novel treatment modalities for a number of diseases including cancer, and stem cells and in particular mesenchymal stem cells (MSCs) have been experimentally used to deliver therapeutic transgenes. However, conflicting reports have on the one side found that human MSCs can promote metastasis, while on the other hand other studies have shown that MSCs can stall the growth of metastatic lesions. In order to clarify the role of MSCs in metastasis development, we tested whether murine MSCs would behave similarly to human cells in mice. We found that the tissue distribution of human and mouse MSCs was nearly identical after intravenous injection. In mice with MDA-MB-231 mammary carcinoma xenografts we found that a fraction of MSCs infiltrated the primary tumor mass, but that the general tissue distribution of MSCs was unaffected by the tumor-burden. About half of the tumor-burdened animals that were treated with murine and human MSCs, respectively, harbored metastatic lesions with only 17% of controls showing metastatic nodules. Hence, both human and mouse MSCs possess metastasis-promoting activity raising concerns about the safe use of MSCs, but at the same time making the use of murine transgenic model systems feasible to study the role of MSCs in metastasis development and possibly finding ways of using them safely as cell therapeutic vehicles.
Insights
Mesenchymal stem cells (MSCs) show metastasis-promoting activity in mice, similar to human cells. This finding raises safety concerns for cell therapy but validates mouse models for studying MSCs in metastasis.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Mesenchymal stem cells (MSCs) are explored for cell therapy, including cancer treatment, due to their potential to deliver therapeutic transgenes.
- Conflicting evidence exists regarding MSCs' role in metastasis, with some studies suggesting promotion and others inhibition of metastatic lesion growth.
Purpose of the Study:
- To investigate whether murine MSCs exhibit similar metastasis-promoting effects as human MSCs in vivo.
- To clarify the role of MSCs in the development of metastasis.
Main Methods:
- Intravenous injection of murine and human MSCs into mice.
- Assessment of MSC tissue distribution after injection.
- Xenograft models using MDA-MB-231 mammary carcinoma cells to evaluate MSCs' effect on primary tumor growth and metastasis.
Main Results:
- Human and murine MSCs displayed nearly identical tissue distribution post-injection.
- A fraction of MSCs infiltrated primary tumors, but overall distribution was unaffected by tumor burden.
- Approximately 50% of tumor-burdened animals treated with MSCs (murine or human) developed metastatic lesions, compared to 17% in controls.
Conclusions:
- Both human and murine MSCs demonstrate metastasis-promoting activity.
- These findings raise concerns regarding the safe clinical application of MSCs in cell therapy.
- The observed effects validate the use of murine models for studying MSCs' role in metastasis and for developing safer therapeutic strategies.
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