Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, traumatic brain and spinal cord injuries, cerebral ...Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, traumatic brain and spinal cord injuries, cerebral stroke, and neurodegenerative diseases. The earlier MOT results in better efficacy in animal models of urgent diseases such as ischemic stroke, and traumatic brain and spinal cord injuries. There is no long-term method to preserve mitochondria. Routine MOT procedure from cell growth to mitochondrial injection often takes serval weeks and is not satisfactory for urgent use cases. Hypothesis: Cryopreserved cells might be mitochondrial donors for MOT. Methods: We isolated mitochondria from cryopreserved human fibroblasts and mesenchymal stem cells (MSCs) in cell banks and compared the mitochondrial viability and transplantation with the mitochondria from fresh cells. Key findings: We found that mitochondria from fresh and cryopreserved cells are comparable in mitochondrial viability and transplantation. We also obtained data showing that mitochondria of fibroblasts and MSCs had similar membrane potential and transfer ability, but MSC’s mitochondria had higher ATP content than fibroblast’s mitochondria. In addition, oxygen consumption rates (OCRs) were higher in MSC’s mitochondria compared to fibroblast’s mitochondria and did not change between fresh and frozen cells. Conclusion: Cryopreserved fibroblasts and MSCs are alternative mitochondrial donors for MOT to fresh cells. MSCs could provide higher ATP-produced mitochondria than fibroblasts.展开更多
COVID-19 severe symptoms and high mortality are mainly seen in elders with age-associated diseases who have mitochondrial dysfunction. Mitochondrial dysfunction is a vulnerability and comorbidity of COVID-19. Cytokine...COVID-19 severe symptoms and high mortality are mainly seen in elders with age-associated diseases who have mitochondrial dysfunction. Mitochondrial dysfunction is a vulnerability and comorbidity of COVID-19. Cytokine storm, and increased serum iron and ferritin and reactive oxygen species (ROS) in COVID-19 further damage mitochondria. Amelioration of mitochondrial dysfunction may be a strategy of prevention and treatment of COVID-19. We also describe mitochondrial organelle transplantation (MOT) which has restored mitochondrial function, improved the repair of injured tissues and suppressed hyperinflammation in life-threatening sepsis. MOT is a potential therapy for severe COVID-19. Finally, we report the first case of MOT for a severe COVID-19 patient. MOT is safe and might have beneficial effect on the severe COVID-19.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">It is known that mitochondrial dysfunction is associated with neurodegenerative diseases including amyotrophic later...<div style="text-align:justify;"> <span style="font-family:Verdana;">It is known that mitochondrial dysfunction is associated with neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Researchers have tested the therapeutic efficacy of many mitochondrial targeted agents;however, results have been disappointing without significant impact on disease survival. Several groups have demonstrated that mitochondrial transfer of isolated normal healthy mitochondria to defective calls can restore functional recovery. Our experience with mitochondria organelle transplantation (MOT) in cancer cells led to investigating the technology for neurodegenerative diseases (NDs), especially ALS. The rationale was that if the uptake of normal mitochondria into cancer cells inhibited proliferation and glycolysis;then MOT might be a cell-based therapy for NDs. In this communication, we will present background research on MOT <span style="white-space:nowrap;"><i>in vitro</i></span> and <span style="white-space:nowrap;"><i>in vivo</i></span> cell culture and animal models respectively. This research evidence showed proof of principle of the technology. This fact led us to try the procedure on a desperate human ALS patient.</span> </div>展开更多
文摘Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, traumatic brain and spinal cord injuries, cerebral stroke, and neurodegenerative diseases. The earlier MOT results in better efficacy in animal models of urgent diseases such as ischemic stroke, and traumatic brain and spinal cord injuries. There is no long-term method to preserve mitochondria. Routine MOT procedure from cell growth to mitochondrial injection often takes serval weeks and is not satisfactory for urgent use cases. Hypothesis: Cryopreserved cells might be mitochondrial donors for MOT. Methods: We isolated mitochondria from cryopreserved human fibroblasts and mesenchymal stem cells (MSCs) in cell banks and compared the mitochondrial viability and transplantation with the mitochondria from fresh cells. Key findings: We found that mitochondria from fresh and cryopreserved cells are comparable in mitochondrial viability and transplantation. We also obtained data showing that mitochondria of fibroblasts and MSCs had similar membrane potential and transfer ability, but MSC’s mitochondria had higher ATP content than fibroblast’s mitochondria. In addition, oxygen consumption rates (OCRs) were higher in MSC’s mitochondria compared to fibroblast’s mitochondria and did not change between fresh and frozen cells. Conclusion: Cryopreserved fibroblasts and MSCs are alternative mitochondrial donors for MOT to fresh cells. MSCs could provide higher ATP-produced mitochondria than fibroblasts.
文摘COVID-19 severe symptoms and high mortality are mainly seen in elders with age-associated diseases who have mitochondrial dysfunction. Mitochondrial dysfunction is a vulnerability and comorbidity of COVID-19. Cytokine storm, and increased serum iron and ferritin and reactive oxygen species (ROS) in COVID-19 further damage mitochondria. Amelioration of mitochondrial dysfunction may be a strategy of prevention and treatment of COVID-19. We also describe mitochondrial organelle transplantation (MOT) which has restored mitochondrial function, improved the repair of injured tissues and suppressed hyperinflammation in life-threatening sepsis. MOT is a potential therapy for severe COVID-19. Finally, we report the first case of MOT for a severe COVID-19 patient. MOT is safe and might have beneficial effect on the severe COVID-19.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">It is known that mitochondrial dysfunction is associated with neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Researchers have tested the therapeutic efficacy of many mitochondrial targeted agents;however, results have been disappointing without significant impact on disease survival. Several groups have demonstrated that mitochondrial transfer of isolated normal healthy mitochondria to defective calls can restore functional recovery. Our experience with mitochondria organelle transplantation (MOT) in cancer cells led to investigating the technology for neurodegenerative diseases (NDs), especially ALS. The rationale was that if the uptake of normal mitochondria into cancer cells inhibited proliferation and glycolysis;then MOT might be a cell-based therapy for NDs. In this communication, we will present background research on MOT <span style="white-space:nowrap;"><i>in vitro</i></span> and <span style="white-space:nowrap;"><i>in vivo</i></span> cell culture and animal models respectively. This research evidence showed proof of principle of the technology. This fact led us to try the procedure on a desperate human ALS patient.</span> </div>
