Human tissue-specific MSCs demonstrate differential mitochondria transfer abilities that may determine their
Swati Paliwal1,2, Rituparna Chaudhuri1, Anurag Agrawal3
1Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi, 110029, India.
Stem Cell Research & Therapy
|November 10, 2018
Summary
Mesenchymal stem cells (MSCs) from different sources have varying mitochondrial donation abilities, linked to their respiratory function. MSCs with higher respiratory capacity show less donation but better suppression of damaging reactive oxygen species in recipient cells.
Area of Science:
- Stem Cell Biology
- Mitochondrial Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) are recognized as potent mitochondrial donors for therapeutic applications.
- MSCs sourced from bone marrow (BM), adipose tissue (AD), dental pulp (DP), and Wharton's jelly (WJ) are used in clinical trials.
- The comparative mitochondrial donor capacity of MSCs from different tissues remains unexplored.
Purpose of the Study:
- To investigate and compare the mitochondrial donor properties of MSCs derived from various tissue sources.
- To determine the correlation between MSC mitochondrial respiratory states and their capacity for mitochondrial transfer.
- To assess the impact of MSC mitochondrial properties on therapeutic efficacy, specifically in suppressing mitochondrial reactive oxygen species (mtROS).
Main Methods:
- Co-culture of labeled MSCs with target cells (U87-MG or rat cardiomyocytes).
- Assessment of mitochondrial transfer using flow cytometry and fluorescence imaging.
- Analysis of mtROS levels via MitoSOX staining and mitochondrial respiration using a Seahorse XF Analyzer.
Main Results:
- Adipose (AD)-MSCs and bone marrow (BM)-MSCs exhibited higher mitochondrial transfer than dental pulp (DP)-MSCs and Wharton's jelly (WJ)-MSCs.
- DP-MSCs and WJ-MSCs were more effective in reducing mtROS in stressed cells compared to AD-MSCs and BM-MSCs.
- A significant inverse correlation was observed between MSC mitochondrial respiration parameters (oxygen consumption, ATP levels, etc.) and their mitochondrial donation capacity.
Conclusions:
- MSCs from different tissues possess distinct mitochondrial respiration capacities, donation potentials, and therapeutic effects.
- MSCs with higher intrinsic respiration show lower mitochondrial transfer but superior mtROS suppression in stressed cells.
- Utilizing MSCs like DP-MSCs or WJ-MSCs with higher respiratory function may offer therapeutic advantages due to enhanced mtROS suppression, even with lower mitochondrial transfer.
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