Study: Mitochondrial transplantation may slow, reverse kidney damage
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Key takeaways:
- Mitochondrial transplantation mitigated AKI for in vitro and ex vivo experiments.
- In vitro tests indicated higher cell proliferative capacity and production.
Mitochondrial transplantation may be effective in mitigating or reversing kidney damage, according to study results from researchers at the Wake Forest University School of Medicine.
“This technology could transform renal transplant medicine,” Giuseppe Orlando, MD, PhD, an associate professor of surgery at Wake Forest University School of Medicine and study co-author, said in a press release. “We provide evidence that mitochondrial transfer lessens the damage renal cells or kidneys may suffer from disease or injury.”
The regenerative process injects healthy mitochondria — membrane-bound cells that produce chemical energy — into diseased or damaged kidney tissue. Researchers tested whether transplanting mitochondrial could alleviate damage in vitro and ex vivo.
In the preclinical trial, researchers collaborated with the University of Turin in Italy and other institutes to preliminarily test human proximal tubular cell cultures, which remove toxins from the kidney. For in vitro experiments, human proximal tubular cells were damaged and then treated with either mitochondria or placebo. Researchers created a porcine model for ex vivo tests that replicated donation after renal transplantation of cardiac death. One kidney received mitochondria, while the other received placebo before being perfused at room temperature for 24 hours. Samples were collected and analyzed at different times.
Mitochondrial transplantation mitigated AKI both in vitro and ex vivo, according to the results. In vitro experiments demonstrated that cells treated with this procedure had higher proliferative capacity and production, preserved organelle polarization and reduced toxicity and reactive oxygen species production. Ex vivo tests indicated greater stability and less damage, while RNA sequencing analysis “showed modulation of genes and pathways most consistent with mitochondrial biogenesis and energy metabolism and downregulation of genes involved in neutrophil recruitment,” Andrea Rossi, PhD, of the department of molecular biotechnology and health science Università di Torino, and colleagues, wrote in the study.
The mitochondrial transplant was “successful in reducing stress in the damaged kidney cells,” according to Orlando, who added the team plans to launch a small pilot study to validate the initial findings and that he is “optimistic that mitochondrial transplantation could one day increase the number of transplantable organs.”
Reference:
Rossi A, et al. Ann Surg. 2023;doi:https://doi.org/10.1097/SLA.0000000000006005.