Ischemia is a term used in medicine to refer to conditions under which organs are deprived of oxygen. Oxygen deprivation causes cells to die and if enough cells die, then the organ is unable to perform its designed function; a condition known as organ failure. Mesenchymal stem cells (MSCs) have been shown in several animal studies to provide significant therapeutic benefit in ischemic organ injuries. Three recent papers have examined the ability of fat-derived MSCs to mitigate ischemic organ damage in lungs, kidneys, and livers. While these studies are in animals, they might provide the foundation for future clinical studies in human patients.
In the first paper (Sun CK, et al., Crit Care Med. 2012 Feb 14), three groups of male rats were either 1) operated on without inducing liver damage; 2) operated on so that the main blood supply to the liver was interrupted for 60 minutes, followed by re-opening the blood supply and treating the rats with fresh culture media that was used to grow the fat-based MSCs; and 3) operated on to cut off the blood supply to the liver for 60 minutes, followed by releasing the blood flow and treatment with fat-derived MSCs at 6 hours and 24 hours after surgery. Three days later, all animals had their livers assayed for damaged, stress and cell death.
In the first group, no sign of liver damage or stress or cell death was observed. In the second group, all the markers for cell death, liver damage and stress were significantly elevated. However in the third group, the markers for cell death, liver damage and stress were significantly lower than those in group two and other markers of liver cell health were increased in the third group relative to the second group.
These results show that fat-derived MSCs preserve liver health and decrease inflammation after ischemic damage to the liver.
The second paper (Furuichi K, et al. Clin Exp Nephrol. 2012 Mar 8), used a similar strategy to examine the ability of fat-derived MSCs to ameliorate kidney function and health after suffering ischemic conditions. Here again, the renal artery to the kidney was clamped for 45 minutes and then injected with either MSCs or buffer at 0, 1, and 2 days after surgery.
The results were a little strange in that the administered MSCs mainly went to the lung. However, those animals that were injected with buffer showed inflammation in the kidney and lots of cell death in the kidney. However those injected with MSCs showed significantly reduced signs of inflammation and greatly reduced amounts of inflammation.
Thus, despite homing to the lung, adipose-derived mesenchymal cells seem to present a reasonable cell-based therapy option for ischemic kidney injury.
Finally, a third paper (Sun CK, et al., J Transl Med. 2011 Jul 22; 9:118), examined the use of fat-derived MSCs to reduce damage during ischemic injury to the lungs. This paper used rats that were divided into three groups. The first group underwent surgery, but no damage was done to the blood supply to the lung. In the second group, the left bronchus of the lung was clamped for 30 minutes, after which the lung was unclamped and the blood allowed to flow for 3 days (known as reperfusion) followed by treatment with fat-derived MSC culture medium. Animals in the third group underwent the same procedure, but were treated with one million and a half fat-derived MSCs at 1, 6, and 24 hours after lung injury. Three days later, animals from all three groups were examined for markers of lung damage and inflammation.
In the first group, the lungs were normal in their function, cell structure, and biochemical markers. No signs of inflammation were observed. The second group, however, had left lung (the one that had been clamped) that worked much more poorly than the right lung. Also, the blood pressure required to push blood through that damaged lobe was much higher in the second group than the other two groups. The more damaged a lung has suffered, the harder it is for the heart to pump blood through it, and the right ventricle much work harder to pump blood through it, which raised the blood pressure in the lung.
The third group showed lungs that worked better and had lower blood pressure than those in the second group. Tissue sections of lungs from group 2 and three animals showed much more damaged in lungs from group two animals than those in group three. Measurement of gene expression in the tissues also showed that lungs from group two animals had much higher levels of genes expressed during inflammation and cell death than those from group three.
This paper presents evidence that fat-derived MSCs might decrease lung damage after ischemic injury.
Trauma to the body from car accidents or work-related injuries can cause organ ischemia. If this damage is significant, acute organ damage can result. Fortunately, fat-derived MSCs are relatively easy to isolate with little additional trauma to the patient. These papers might provide the impetus for future preclinical experimental and, eventually, clinical trials in human patients to alleviate ischemic damage to organs in accident victims.