Stem cell fluid shows promise as PAH treatment, study finds
Medium reduces PAH signs in rat, cell studies
Stem cell-derived conditioned medium, or the liquid that remains after cells are cultured, reduces the signs of pulmonary arterial hypertension (PAH) in rat and cell models, a study showed.
“These findings support [stem cell]‐derived conditioned medium as a promising therapeutic strategy for PAH, warranting further investigation in translational studies and clinical trials,” the researchers wrote.
The study, “IPSC-Derived Conditioned Medium Reduces Oxidative Stress and Vascular Remodeling in Rat Models of Pulmonary Arterial Hypertension,” was published in the Journal of Cellular Physiology.
PAH is characterized by narrowing of the pulmonary arteries, blood vessels that supply the lungs. This narrowing restricts blood flow, boosts blood pressure, and makes it harder for the right side of the heart to pump blood. Blood vessel narrowing is driven by pulmonary vascular remodeling, the excessive growth of cells that line blood vessels, particularly the pulmonary artery smooth muscle cells (PASMCs).
Induced pluripotent stem cell-derived conditioned medium, or iPSC-CM, is the liquid that remains after iPSCs, or cells reprogrammed from adult cells, are cultured. It contains proteins, growth factors, and other molecules, with the potential to modulate cellular processes and promote tissue repair.
Studies point to ‘promising’ approach to PAH treatment
Researchers in Taiwan investigated the therapeutic potential of iPSC-CM in a rat model of PAH and in PASMCs.
When the team treated PAH rats with iPSC-CM via daily abdominal infusions, the right ventricular systolic pressure — the blood pressure in the right side of the heart during a heartbeat — was significantly reduced. Treatment also mitigated right ventricular hypertrophy, the abnormal enlargement and thickening of the right ventricle in the heart. These benefits were independent of the timing of iPSC-CM infusions — before (prophylactic group) or two weeks after (treatment group) PAH-like disease was induced.
Tissue analysis also revealed that iPSC-CM attenuated the thickening of the pulmonary arterial walls.
At the molecular level, iPSC-CM lowered the production of two drivers of pulmonary vascular remodeling in lung tissues: hypoxia-inducible factor 1-alpha (HIF-1-alpha) and platelet-derived growth factor-BB (PDGF-BB). Treatment also reduced signs of oxidative stress, a type of tissue damage caused by an imbalance between reactive oxygen species and the body’s ability to neutralize them.
In cells, iPSC-CM suppressed the growth and migration of PASMCs under conditions of low oxygen (hypoxia) and stimulation with PDGF-BB. Treatment also lowered the production of reactive oxygen species in PASMCs and inactivated a pathway called PAK‐1/AKT, thereby reducing HIF-1-alpha.
“These findings support iPSC-CM as a promising acellular approach for targeting vascular remodeling and oxidative stress in PAH, warranting further investigation toward clinical translation,” the researchers wrote. “Future studies should also evaluate scalability, manufacturing stability, and delivery strategies to facilitate clinical application.”
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