Mitochondrial Transplantation as a Treatment for Kidney Damage

It is interesting see an increased focus on assessing the ability of mitochondrial transplantation to be useful in a variety of circumstances, not just as a treatment to reduce the mitochondrial dysfunction that occurs with aging. The limiting factor in bringing mitochondrial transplantation to the clinic is chiefly the speed at which the research and development communities can achieve the logistical advances needed to reliably produce enough mitochondria to deliver to an entire organ (at first), and the whole body (later). It is likely the case that mitochondria will have to be patient-matched by haplotype of mitochondrial DNA, which further multiplies the size of the necessary infrastructure. Several biotech startups are working on this challenge, and the research community anticipates that present small tests will point the way to later clinical trials, once it is possible to manufacture sufficient mitochondria in a cost-effective way.

Today's research materials provide an example of one such small test of mitochondrial transplantation, focused on the treatment of kidney damage in the context of disease and transplantation. It is possible that mitochondrial transplantation can be used to greatly improve the quality of donor organs, reducing the cell death and damage resulting from the stresses of the transplantation process. Though not the focus of the research here, good results in this context also suggest that mitochondrial transplantation would be useful as a treatment for acute kidney injury.

Study Shows Mitochondrial Transplantation Effective in Reversing Damage to Kidneys and Kidney Cells

Mitochondrial transplantation is a regenerative medicine technology where healthy mitochondria are taken from cultured cells or tissue from organ donors and then injected into a diseased or damaged tissue or organ. Mitochondria produce the energy needed for a cell to function. "Here, we provide evidence that mitochondrial transfer lessens the damage that renal cells or the kidneys may suffer from disease or injury." For the study, the research team conducted preliminary tests in cultures of human proximal tubular cells, which are found in the kidneys and play an important in removing toxins. When the damaged cells were exposed to healthy mitochondria, cellular energy increased, and toxicity decreased.

Additional research found that kidneys injected with healthy mitochondria showed signs of recovery. These results are significant because in the U.S., 20% of the kidneys procured for transplantation are eventually discarded because they are too damaged, and this potential new treatment may help. This is especially true in a new type of organ donation called "uncontrolled donation after cardiac death," an area of active research. In this setting, the kidneys do not receive adequate blood supply, and mitochondria and the kidneys are damaged.

Mitochondria Transplantation Mitigates Damage in an In Vitro Model of Renal Tubular Injury and in an Ex Vivo Model of DCD Renal Transplantation

Mitochondrial transplantation (MITO) is a process where exogenous isolated mitochondria are taken up by cells. As virtually any morbid clinical condition is characterized by mitochondrial distress, MITO may find a role as a treatment modality in numerous clinical scenarios including acute kidney injury (AKI).

In vitro, cells treated with MITO showed higher proliferative capacity and ATP production, preservation of physiological polarization of the organelles and lower toxicity and reactive oxygen species production. Ex vivo, kidneys treated with MITO shed fewer molecular species, indicating stability. In these kidneys, pathology showed less damage while RNAseq analysis showed modulation of genes and pathways most consistent with mitochondrial biogenesis and energy metabolism and downregulation of genes involved in neutrophil recruitment