Ascorbic acid delivered by mesoporous silica nanoparticles induces the differentiation of human embryonic stem cells into cardiomyocytes

• Published in: Materials Science and Engineering C: Biomimetic and Supramolecular Systems Vol. 56; pp. 348 - 355
• Main Authors: Ren, Mingming, Han, Zhen, Li, Jinglai, Feng, Gang, Ouyang, Shuyuan
• Format: Journal Article
• Language: English
• Published: Netherlands 01.11.2015
• Subjects: Ascorbic acid; Ascorbic Acid - pharmacology; Cell Differentiation - drug effects; Cell Line; Differentiation; Drug Delivery Systems - methods; Genes; Human; Human Embryonic Stem Cells - cytology; Human Embryonic Stem Cells - metabolism; Humans; Kinases; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Nanoparticles - chemistry; Nanostructure; Porosity; Silicon Dioxide - chemistry; Silicon Dioxide - pharmacology; Stem cells; Tissue engineering; Human embryonic stem cells; Mesoporous silica nanoparticles; Cardiomyocytes; Ascorbic acid; Differentiation
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2015.06.048

Embryonic stem (ES) cells offer the potential to generate all cell types in the body, which provide a promising approach to repair tissue damage or dysfunction. In the past decade, great efforts have been made to induce the differentiation of ES cells into numerous types of cells, such as adipocytes, neurocytes and cardiomyocytes. However, the low differentiated efficiency and successful rate limit the development of induction of the differentiation of stem cells for tissue engineering. Here, we utilize ascorbic acid (AA)-loaded fluorescent TRITC-mesoporous silica nanoparticles (TMSN-AA) as a potential tool to induce the differentiation of human ES cells into cardiomyocytes. The treatment of human ES cells by TMSN-AA nanoplex arrests cell cycle at G1 phase and decreases the expression of stemness genes octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2), which exhibits more significant induction efficiency of stem cell differentiation than the treatment by AA alone. Furthermore, we have tested the myocardial marker genes cardiac Troponin I (cTnI) and fetal liver kinase 1 (FLK-1), and found these genes are up-regulated by TMSN-AA nanoplex. Importantly, this work demonstrates the more efficient induction efficiency of human ES cells differentiation by the nanoparticle-drug formulation. Our studies reveal a novel approach based on MSNs as nanocarriers to induce the differentiation of human ES cells into cardiomyocytes efficiently and feasibly, and offer the potential perspectives for tissue engineering, eventually in clinical applications.