Effects of genetically engineered mitochondria treatment on proliferation enhancement of MSCs

Abstract

Mesenchymal stem cells (MSCs) can be differentiated into different lineages under the appropriate induction conditions. Thus, MSCs have enormous potential for cell therapy and have been shown to be capable of differentiation into neural fates. Therefore, MSC transplantation is the preferred treatment for neurodegenerative diseases. However, MSCs have several disadvantages, such as limited proliferative capacity. Abnormal mitochondrial morphology and functions have been discovered in neurodegenerative diseases, such as Parkinson’s disease, raising the importance of research on mitochondria in neurodegenerative diseases. Thus, this study hypothesized that a positive therapeutic effect in neurodegenerative diseases could be expected in response to the transplantation of MSCs injected with healthy mitochondria into the injury site. First, I verified whether the isolated mitochondria were delivered into MSCs. After treating the mitochondria, I evaluated the proliferative capacity of MSCs using MTS assay and cell counting assay. I compared mitochondrial contribution to MSCs proliferation and survival between HEK293 cells and hiPSCs. The results showed that hiPSCs mitochondria contributed more to MSC proliferation and survival than those of the HEK293 cells. In addition, I produced genetically engineered cell lines targeting the inner and outer mitochondrial membrane proteins in each cell, and then, isolated and treated the mitochondria to MSCs. Based on the results, I suggest the possibility that mitochondria can also serve as carriers to deliver genes without toxicity to target cells.