Study reveals a ‘reconditioning’ process that increases stem cells ability to treat ARDS

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A study released today in STEM CELLS Translational Medicine (SCTM) demonstrates how preconditioning mesenchymal stem cells (MSCs) enhances their ability to treat acute respiratory distress disorder (ARDS).

Ben Antebi, PhD

A study released today 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 effective MSC 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 phase, 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.”

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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.

About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (http://www.StemCells.com), celebrating its 37th year, is the world's first journal devoted to this fast paced field of research. The Oncologist® (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 24th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

About Regenerative Medicine Foundation (RMF): The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honouring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.

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