MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function

• DOI: 10.1038/srep09073
• Publication Date: 2015-03-13T10:53:03Z
• Authors: Andrés Caicedo; Vanessa Fritz; Jean-Marc Brondello; Mickaël Ayala; Indira Dennemont; Naoill Abdellaoui; Florence de Fraipont; Anaïck Moisan; Claire Angebault ...; Hassan Boukhaddaoui; Christian Jorgensen; Marie-Luce Vignais
• Keywords: 0303 health sciences; [SDV]Life Sciences [q-bio]; 610; Reproducibility of Results; Mesenchymal Stem Cells; 612; Flow Cytometry; Time-Lapse Imaging; Article; Coculture Techniques; Mitochondria; 3. Good health; 03 medical and health sciences; Adenosine Triphosphate; Cell Movement; Cell Line, Tumor; Neoplasms; Humans; Metabolomics; Cell Proliferation

AbstractMitochondrial activity is central to tissue homeostasis. Mitochondria dysfunction constitutes a hallmark of many genetic diseases and plays a key role in tumor progression. The essential role of mitochondria, added to their recently documented capacity to transfer from cell to cell, obviously contributes to their current interest. However, determining the proper role of mitochondria in defined biological contexts was hampered by the lack of suitable experimental tools. We designed a protocol (MitoCeption) to directly and quantitatively transfer mitochondria, isolated from cell type A, to recipient cell type B. We validated and quantified the effective mitochondria transfer by imaging, fluorescence-activated cell sorting (FACS) and mitochondrial DNA analysis. We show that the transfer of minute amounts of mesenchymal stem/stromal cell (MSC) mitochondria to cancer cells, a process otherwise occurring naturally in coculture, results in cancer cell enhanced oxidative phosphorylation (OXPHOS) activity and favors cancer cell proliferation and invasion. The MitoCeption technique, which can be applied to different cell systems, will therefore be a method of choice to analyze the metabolic modifications induced by exogenous mitochondria in host cells.