Cardiac commitment driven by MyoD expression in pericardial stem cells.

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.

Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.

Tissue damage often induces local inflammation that in turn dictates a series of subsequential responses, such as stem cell activation and growth, to maintain tissue homeostasis. The aim of the study is to testify the possibility of using inflammation-trained stem cells as optimal donor cells to augment the efficacy of cell therapy. The pericardial stem/stromal cells derived from the animals after myocardial infarction (MI-pSC) showed an enhanced myogenic potential and augmented reparative activity after transplantation in the injured hearts, as compared to the Sham-pSC. Bulk RNA-Seq analysis revealed significant upregulation of a panel of myogenic and trophic genes in the MI-pSC and, notably, Sfrp1 as an important anti-apoptotic factor induced robustly in the MI-pSC. Injection of the MI-pSC yielded measurable numbers of surviving cardiomyocytes (Tunel and Casp-3 negative) within the infarct area, but the effects were significantly diminished by siRNA-based silence of Sfrp1 gene in the pSC. Primed Sham-pSC with pericardial fluid from MI rats mimicked the upregulation of Sfrp1 and enhanced myogenic potential and reparative activity of pSC. Taken together, our results illustrated the inflammation-trained pSC favor a reparative activity through upregulation of Sfrp1 gene that confers anti-apoptotic activity in the injured cardiomyocytes. Therefore, the active form of stem cells may be used as a cardiac protective agent to boost therapeutical potential of stem cells.

Pharmacological Activities of Ginkgolic Acids in Relation to Autophagy.

Plant-derived natural compounds are widely used as alternative medicine in healthcare throughout the world. Ginkgolic acids, the phenolic compounds isolated from the leaves and seeds of Ginkgo biloba, are among the chemicals that have been explored the most. Ginkgolic acids exhibit cytotoxic activity against a vast number of human cancers in various preclinical models in vitro and in vivo. Additionally, the pharmacological activities of ginkgolic acids are also involved in antidiabetic, anti-bacteria, anti-virus, anti-fibrosis, and reno/neuroprotection. Autophagy as a highly conserved self-cleaning process that plays a crucial role in maintaining cellular and tissue homeostasis and has been proven to serve as a protective mechanism in the pathogenesis of many diseases, including neurodegenerative diseases, cancer, and infectious diseases. In this review, we surveyed the pharmacological activities of the major three forms of ginkgolic acids (C13:0, C15:1, and C17:1) that are linked to autophagic activity and the mechanisms to which these compounds may participate. A growing body of studies in last decade suggests that ginkgolic acids may represent promising chemical compounds in future drug development and an alternative remedy in humans.