Format

Send to

Choose Destination
Molecules. 2018 Mar 19;23(3). pii: E687. doi: 10.3390/molecules23030687.

Miro1 Enhances Mitochondria Transfer from Multipotent Mesenchymal Stem Cells (MMSC) to Neural Cells and Improves the Efficacy of Cell Recovery.

Author information

1
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. nucleus-90@yandex.ru.
2
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. nucleus-90@yandex.ru.
3
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. silachevdn@genebee.msu.ru.
4
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. silachevdn@genebee.msu.ru.
5
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. popkov.vas@gmail.com.
6
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. popkov.vas@gmail.com.
7
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. lju_2003@list.ru.
8
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. lju_2003@list.ru.
9
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. irinapevzner@mail.ru.
10
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. irinapevzner@mail.ru.
11
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. plotnikov@belozersky.msu.ru.
12
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. plotnikov@belozersky.msu.ru.
13
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia. plotnikov@belozersky.msu.ru.
14
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. gtsukhikh@mail.ru.
15
Department of obstetrics, gynecology, perinatology and reproduction, Sechenov First Moscow State Medical University, 119991 Moscow, Russia. gtsukhikh@mail.ru.
16
A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. zorov@genebee.msu.ru.
17
V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia. zorov@genebee.msu.ru.

Abstract

A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain.

KEYWORDS:

astrocyte; ischemia; mitochondria; stroke; tunneling nanotubes

PMID:
29562677
PMCID:
PMC6017474
DOI:
10.3390/molecules23030687
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center