Atrial myxomas arise from multipotent cardiac stem cells.

Area of Science:

• Cardiology
• Stem Cell Biology
• Oncology

Background:

• Cardiac myxomas are rare, benign heart tumors of uncertain origin.
• These tumors are composed of a myxoid matrix and stromal cells.
• Cardiac tumors are valuable research models due to their rarity and presentation.

Purpose of the Study:

• To investigate whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue.
• To analyze the characteristics of CSCs within cardiac myxomas.
• To determine the potential of myxoma-derived CSCs in tumor formation.

Main Methods:

• Analysis of 23 human cardiac myxomas for multipotent CSCs.
• Detection of c-kit positive cells and assessment of their lineage commitment (CD45, CD31).
• In vitro studies on myxoma-derived CSCs for stemness properties and matrix secretion.
• Transcriptome analysis of myxoma-derived CSCs compared to normal CSCs.
• Xenograft studies in immunodeficient mice to assess tumor-initiating potential.

Main Results:

• Cardiac myxomas contain c-kit positive cells, with a subset (c-kitpos/CD45neg/CD31neg) expressing stemness and cardiac progenitor markers.
• These specific myxoma-derived CSCs secrete key matrix components (chondroitin-6-sulfate, hyaluronic acid) and exhibit stem cell properties in vitro.
• Myxoma-derived CSCs show a transcriptome similar to normal CSCs but with specific dysregulated miRNAs.
• Myxoma-derived CSCs, unlike normal CSCs, can initiate human myxoma tumor formation in xenografts.

Conclusions:

• Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs meet the criteria for atrial myxoma-initiating stem cells.
• The transcriptome suggests these cells are related to atrial multipotent CSCs.
• Human cardiac myxomas may represent the first identified CSC-related human heart disease.