Abstract
BackgroundRecent studies have demonstrated mesenchymal stem cells (MSCs) as effective mitochondrial donors with therapeutic success in multiple experimental models of human disease. MSCs obtained from different tissue sources such as bone marrow (BM), adipose (AD), dental pulp (DP), and Wharton’s jelly (WJ) are routinely used in clinical trials with no known study of their mitochondrial donor capacity. Here, we show for the first time that MSCs derived from different tissue sources have different mitochondrial donor properties and that this is correlated with their intrinsic respiratory states.MethodsMitoTracker®-labeled MSCs were co-cultured with Cell Trace–labeled U87-MG cells or rat cardiomyocytes. Mitochondrial transfer abilities of MSCs were assessed by using flow cytometry analysis and fluorescence imaging. Mitochondrial reactive oxygen species (mtROS) levels were analyzed by using MitoSOX red–based staining, and mitochondrial respiration parameters were analyzed by using a Seahorse XF Analyzer.ResultsAD-MSCs and BM-MSCs displayed higher mitochondrial transfer than DP-MSCs and WJ-MSCs. Counterintuitively, DP-MSCs and WJ-MSCs were more effective in suppressing mtROS levels in stressed recipient cells than AD-MSCs or BM-MSCs. Interestingly, the oxygen consumption rates and intrinsic mitochondrial respiration parameters like ATP levels, basal and maximal respiration, and mitochondrial DNA copy number in donor MSCs showed a highly significant inverse correlation with their mitochondrial donation.ConclusionsWe find that there are intrinsic differences in the mitochondrial respiration, donation capacity, and therapeutic efficacy among MSCs of different tissue origin. MSCs with high mitochondrial respiration capacities are associated with lower mitochondrial transfer but more effective suppression of mtROS in stressed recipient cells. This is most compatible with a model where recipient cells optimally regulate mitochondrial transfer such that they take more mitochondria from MSCs with lower mitochondrial function. Furthermore, it appears to be advantageous to use MSCs such as DP-MSCs or WJ-MSCs with higher mitochondrial respiratory abilities that achieved better therapeutic effect with lower mitochondrial transfer in our study. This opens up a new direction in stem cell therapeutics.
Highlights
Recent studies have demonstrated mesenchymal stem cells (MSCs) as effective mitochondrial donors with therapeutic success in multiple experimental models of human disease
We investigate the differential mitochondria transfer abilities of MSCs derived from bone marrow (BM)-MSC, AD-MSC, dental pulp (DP)-MSC, and Wharton’s jelly (WJ)-MSC sources to stressed U87-MG cells or rat cardiomyocytes, treated with antimycin
Successful mitochondria transfer from tissue-specific MSCs to U87-MG cells and cardiomyocytes was observed when MSCs were co-cultured with the recipient cells
Summary
Recent studies have demonstrated mesenchymal stem cells (MSCs) as effective mitochondrial donors with therapeutic success in multiple experimental models of human disease. Damaged mitochondria and mitochondrial products such as damage-associated molecular patterns (DAMPs) are released as stress signals during cellular injury These factors, along with elevated levels of reactive oxygen species levels, signal the MSCs to enhance their bioenergetics and initiate mitochondria donation to injured recipient cells [10, 11]. Studies have shown that these MSCs from these different tissue origins demonstrate the ability to transfer mitochondria to rescue damaged cells and restore respiratory potential in recipients [17, 23]. We have compared the rescue potential of tissue-specific MSCs indicated by their abilities to reduce mitochondrial reactive oxygen species (mtROS) levels in recipient cells under oxidative stress. This study suggests that mitochondrial parameters of tissue-specific MSCs are critical variables in determining the optimum tissue source of MSCs for regenerative therapy purposes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
