One of the ways in which transplanted stem cells aid native cells in the short period of time before they die is by transferring mitochondria. This happens in much the same way as the cells also transfer signals via extracellular vesicles. A mitochondrion and a vesicle are both membrane-wrapped packages of molecules, albeit that the former is much more complex and functional. Mitochondria are important to cell function, as they generate the chemical energy store molecule adenosine triphosphate (ATP) required to power the cell.
Unfortunately, loss of mitochondrial function occurs with age, and is thought to be an important component of degenerative aging. The roots of age-related mitochondrial dysfunction are complex, involving damage to mitochondrial DNA, epigenetic changes that alter the expression of important mitochondrial genes, failure of the quality control mechanisms of mitophagy, and so forth. Transferring in new, youthful mitochondria harvested from cell cultures has been shown to help, and a few companies are working on the manufacturing techniques needed to make this form of therapy a reality. What if existing stem cell therapies could be made more effective as a vector for the provision of new mitochondria, however? That question is explored in today's open access paper, a followup to work published last year.
Intercellular mitochondrial transfer has emerged as a fundamental biological process whereby cells exchange mitochondria to mitigate stress and promote tissue repair, an extension of mitochondrial movement and cellular communication. Occurring in a wide variety of cells, this innate mechanism has the potential to be co-opted to support local energy demands where existing mitochondrial networks struggle. Mesenchymal stem cells (MSCs) display a particular propensity for initiating mitochondrial transfer to nearby cells; their mitochondria enhance cellular respiration, induce cell reprogramming, and repair metabolic function in recipient cells. Due to their lower energy demands, MSCs are favored for mitochondrial transfer to diseased cells with high bioenergetic needs. Their immune privilege, availability from various sources, and ease of use render MSCs ideal donor cells for delivering healthy mitochondria.
However, despite growing recognition of the therapeutic potential of mitochondrial transfer, its widespread adoption is hindered by limited rates of mitochondrial translocation. Existing methods to enhance transfer rates-such as overexpressing mechanistic proteins like the motor protein Miro1 and gap junction Cx43, or engineered techniques like MitoCeption and MitoPunch, are cumbersome and labor-intensive. Consequently, despite advances in understanding intercellular mitochondrial transfer, current therapeutic strategies often fall short due to limited efficacy and challenges in delivery, underscoring the need for new approaches.
To address these limitations, we have developed a biomaterial-based therapeutic strategy employing molybdenum disulfide (MoS2) nanoflowers with atomic-scale modifications to transform human mesenchymal stem cells (hMSCs) into mitochondrial biofactories. The increased mitochondrial content within MSCs enhances their capacity for intercellular mitochondrial transfer via tunneling nanotubes (TNTs). Utilizing nanomaterial platforms allows us to bypass limitations in transfer rates and eliminates the need for complex genetic interventions or extensive use of systemically administered drugs targeting mitochondrial function. This method capitalizes on the natural propensity of MSCs to transfer mitochondria, amplifying this capability through available mitochondrial mass. Our findings underscore the potential of nanomaterial-enhanced intercellular mitochondrial transfer as a viable therapeutic option for treating a wide range of mitochondrial dysfunctions.
View the full article at FightAging
