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Updated: Jun 4, 2025
In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
An autocrine synergistic desmin-SPARC network promotes cardiomyogenesis in cardiac stem cells
Lucia Leitner1, Martina Schultheis1, Franziska Hofstetter1
1Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Department of Molecular Biology, Vienna, Austria.
Insights
Cardiac stem cells use desmin and SPARC to promote heart repair. This interaction forms a feedback loop, suggesting stem cells secrete factors like SPARC to maintain heart health throughout life.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Molecular Cardiology
Background:
- Mammalian hearts possess cardiac stem cells, but their in vivo repair potential remains untapped.
- The proteins desmin and SPARC are known to influence cardiomyogenesis during embryonic development.
- Cardiac stem cells' role in adult heart homeostasis is not fully understood.
Purpose of the Study:
- To investigate the cooperative roles of desmin and SPARC in cardiac stem and progenitor cell cardiomyogenesis.
- To elucidate the mechanisms by which desmin and SPARC interact to promote heart cell formation.
- To explore the potential of cardiac stem cells as a source of factors for cardiac repair.
Main Methods:
- Utilized mouse embryonic and cardiac stem cell lines for in vitro modeling.
- Analyzed gene expression and protein secretion of desmin and SPARC.
- Investigated the effects of SPARC on cardiomyogenesis and cardiac transcription factors.
Main Results:
- Desmin promotes cardiomyogenesis non-cell-autonomously by increasing SPARC secretion.
- Secreted SPARC acts in an autocrine manner on cardiac stem cells, upregulating myocardial transcription factors and desmin.
- A positive feedback loop between desmin and SPARC was identified, with SPARC negatively regulating its own mRNA.
- Paracrine SPARC rescues desmin-haploinsufficiency and promotes cardiomyogenesis in a glycosylation-dependent manner.
Conclusions:
- Desmin and SPARC form a critical genetic interaction promoting cardiomyogenesis in cardiac stem cells.
- Cardiac stem cells may function as glands, secreting SPARC to maintain cardiac homeostasis and modulate age-related changes.
- This study highlights a novel mechanism for endogenous cardiac repair and suggests therapeutic potential for SPARC-based strategies.
Abstract:
The mammalian heart contains cardiac stem cells throughout life, but it has not been possible to harness or stimulate these cells to repair damaged myocardium in vivo. Assuming physiological relevance of these cells, which have evolved and have been maintained throughout mammalian evolution, we hypothesize that cardiac stem cells may contribute to cardiomyogenesis in an unorthodox manner. Since the intermediate filament protein desmin and the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) promote cardiomyogenic differentiation during embryogenesis in a cell-autonomous and paracrine manner, respectively, we focus on their genes and employ mouse embryonic and cardiac stem cell lines as in vitro models to ask whether desmin and SPARC cooperatively influence cardiomyogenesis in cardiac stem and progenitor cells. We show that desmin also promotes cardiomyogenesis in a non-cell autonomous manner by increasing the expression and secretion of SPARC in differentiating embryonic stem cells. SPARC is also secreted by cardiac stem cells where it promotes cardiomyogenesis in an autocrine and concentration-dependent manner by upregulating the expression of myocardial transcription factors and its elicitor desmin. Desmin and SPARC interact genetically, forming a positive feedback loop and secreted autocrine and paracrine SPARC negatively affects sparc mRNA expression. Paracrine SPARC rescues cardiomyogenic desmin-haploinsufficiency in cardiac stem cells in a glycosylation-dependent manner, increases desmin expression, the phosphorylation of Smad2 and induces the expression of gata4, nkx2.5 and mef2C. Demonstration that desmin-induced autocrine secretion of SPARC in cardiac stem cells promotes cardiomyogenesis raises the possibility that a physiological function of cardiac stem cells in the adult and aging heart may be the gland-like secretion of factors such as SPARC that modulate age-related and adverse environmental influences and thereby contribute to cardiac homeostasis throughout life.
