|A study released in STEM CELLS Translational Medicine (SCTM) demonstrates how preconditioning mesenchymal stem cells (MSCs) enhances their ability to treat acute respiratory distress disorder (ARDS). This important information could point to a way to developing more effectiveMSC treatments for clinical application, according to Ben Antebi, Ph.D., who led the team of investigators from the U.S. Army Institute of Surgical Research and Stanford University.|
ARDS — a life-threatening condition in which fluid accumulates in the lung — has a mortality rate of up to 46 percent. It can result from a variety of conditions including pneumonia, sepsis, drug overdose and more. However, the majority of ARDS cases are due to burn injuries – especially those involving smoke inhalation. ARDS is of particular interest to the military, as it is a significant complication in combat casualty care today.
Currently no drug has proven effective in treating ARDS. Studies show, however, that treatment with MSCs collected from bone marrow improves fluid clearance in the lungs and decreases their permeability, while also combatting infection and inflammation. Researchers believe this is due to a key feature of ARDS — an imbalance between pro- and anti-inflammatory mediators in the body known as cytokines. MSCs are known to balance key inflammatory cytokines (TNF-α, IL-1RA, IL-6, IL-10) and secrete lipid compounds, as well as modulate other immune cells, which is why they might prove beneficial as an ARDS treatment.
A major drawback to this, however, is the fate of the MSCs following exposure to a hostile microenvironment, such as in ARDS. One proposed solution is to “recondition” the MSCs prior to treatment in serum coming from subjects with ARDS.
The study reported on in SCTM looks at how that might work. In its first , a group of pigs suffering from ARDS (due to smoke inhalation and burns) were treated with MSCs. A group of uninjured, untreated pigs and another group comprised of untreated ARDS-injured pigs were used as controls. In the second phase, serum was collected from the three groups of pigs to “recondition” the pigs’ MSCs ex vivo (in the lab). In the study’s third and final phase, the methods were repeated using human MSCs and lipopolysaccharide, which induces inflammation-like ARDS in vitro (in the body).
When each group of animals was analyzed for expression of the inflammatory mediators, phase 1 results showed that allogeneic MSC treatment was able to regulate the ARDS symptoms. Interestingly, outcomes from phase 2 showed that preconditioning MSCs with serum from subjects with untreated ARDS had a negative impact on how the cells functioned while, conversely, Dr. Antebi reported, “We found that MSCs reconditioned with serum previously exposed to MSCs enhanced their regenerative function. In addition to the known paracrine function of MSCs, we demonstrate that MSCs stimulate themselves via autocrine mechanisms. This leads us to conclude that this ‘pre-exposure’ technique can be used to augment MSC function for use in clinical applications in treating ARDS,” he said.
“Altogether, our results demonstrate a method for controlling the rapid progression of ARDS,” added Amy Xu, the paper’s first author. “This is especially pertinent in combat settings where extensive medical resources are not immediately available.”
“These study results give us new insight into the therapeutic function of bone marrow mesenchymal stem cells and how reconditioning them in their own serum enhances their regenerative function,” said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “While this work could someday be used for patients with acute respiratory distress, other clinical applications may also benefit from this strategy.”
The full article, “Mesenchymal stem cells re-conditioned in their own serum exhibit augmented therapeutic properties in the setting of acute respiratory distress syndrome,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/sctm.18-0236.