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Related Concept Videos

Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
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Mesenchymal Stem Cell Extracellular Vesicles Reverse Sugen/Hypoxia Pulmonary Hypertension in Rats.

James R Klinger1,2, Mandy Pereira3, Michael Del Tatto3

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|November 14, 2019
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Mesenchymal stem cell extracellular vesicles can prevent and reverse pulmonary hypertension in rats. These vesicles reduce lung inflammation and promote blood vessel growth, offering a potential new treatment for pulmonary arterial hypertension.

Keywords:
exosomemacrophagemicroRNApulmonary vascular remodelingright ventricular hypertrophy

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Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
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Area of Science:

  • Regenerative Medicine
  • Cardiovascular Research
  • Cell Biology

Background:

  • Pulmonary hypertension (PH) is a severe condition with limited treatment options.
  • Mesenchymal stem cell extracellular vesicles (MSC-EVs) show promise in treating PH, but their efficacy in established disease and underlying mechanisms require further investigation.
  • Understanding the therapeutic potential of MSC-EVs in larger animal models is crucial for clinical translation.

Purpose of the Study:

  • To evaluate the efficacy of MSC-EVs in preventing and reversing Sugen/hypoxia-induced pulmonary hypertension in rats.
  • To elucidate the mechanisms by which MSC-EVs exert their therapeutic effects on pulmonary hypertension.
  • To determine the optimal dosage and administration intervals for MSC-EV treatment in a preclinical PH model.

Main Methods:

  • Rats were induced with pulmonary hypertension using Sugen 5416 and hypoxia.
  • Mesenchymal stem cell extracellular vesicles or saline vehicle were administered intravenously before or after PH induction.
  • Pulmonary hypertension was assessed by measuring right ventricular systolic pressure, cardiac hypertrophy, and pulmonary vessel muscularization.
  • Immunohistochemistry was used to analyze macrophage activation states (M1/M2 ratio) and recruitment in lung tissue.

Main Results:

  • MSC-EV treatment, administered before or after PH induction, normalized right ventricular pressure and reduced right ventricular hypertrophy.
  • MSC-EVs significantly decreased the muscularization of peripheral pulmonary vessels.
  • Treatment was associated with reduced lung macrophage infiltration, an increased M2/M1 macrophage ratio, and enhanced peripheral blood vessel density.
  • The therapeutic effects were observed across a range of MSC-EV doses and administration intervals.

Conclusions:

  • Mesenchymal stem cell extracellular vesicles are effective in both preventing and reversing established pulmonary hypertension in a rat model.
  • MSC-EVs exert their therapeutic effects by modulating the lung immune microenvironment, specifically by promoting an anti-inflammatory M2 macrophage phenotype and enhancing vascular repair.
  • These findings suggest that MSC-EVs hold significant potential as a novel therapeutic strategy for pulmonary arterial hypertension.