Autophagy modulation effect on homotypic transfer of intracellular components via tunneling nanotubes in mesenchymal stem cells.

Autor: Sadeghsoltani F; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, 5166614766, Iran., Avci ÇB; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Hassanpour P; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, 5166614766, Iran., Haiaty S; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Rahmati M; Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, 5166614766, Iran., Mota A; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. mota.biomed@gmail.com.; Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, 5166614766, Iran. mota.biomed@gmail.com., Rahbarghazi R; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. rahbarghazir@tbzmed.ac.ir.; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 5166653431, Iran. rahbarghazir@tbzmed.ac.ir., Nemati M; Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran., Mahdipour M; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Talebi M; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Takanlou LS; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Takanlou MS; Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey., Mehdizadeh A; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2024 Jul 02; Vol. 15 (1), pp. 189. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1186/s13287-024-03813-1
Abstrakt: Background: Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation.
Methods: MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography.
Result: Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p < 0.05). Western blotting revealed the significant reduction of Rab8 and p-FAK in 3-MA-treated MSCs (p < 0.05), indicating the inhibition of TNT assembly and vesicle transport. Likewise, the stimulation of autophagy increased autophagic flux and mitochondrial membrane integrity compared to 3-MA-treated MSCs. Despite these findings, protein levels of mitochondrial membrane Miro1 and 2 were unchanged after autophagy inhibition/stimulation (p > 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator.
Conclusions: In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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