Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs—namely, directed differentiation and the paracrine function—in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.
Stem cells are undifferentiated cells that can give rise to any types of cells in our body. Hence, they have been utilized for various applications, such as drug testing and disease modeling. However, for the successful of those applications, the survival and differentiation of stem cells into specialized lineages should be well controlled. Growth factors and chemical agents are the most common signals to promote the proliferation and differentiation of stem cells. However, those approaches holds several drawbacks such as the negative side effects, degradation or denaturation, and expensive. To address such limitations, nanomaterials have been recently used as a better approach for controlling stem cells behaviors. Graphene oxide is the derivative of graphene, the first two-dimensional (2D) materials in the world. Recently, due to its extraordinary properties and great biological effects on stem cells, many scientists around the world have utilized graphene oxide to enhance the differentiation potential of stem cells. In this mini review, we highlight the key advances about the effects of graphene oxide on controlling stem cell growth and various types of stem cell differentiation. We also discuss the possible molecular mechanisms of graphene oxide in controlling stem cell growth and differentiation.
Angiogenesis, a process of new blood vessel formation from existing blood vessels, plays an important role in tumor growth and the tissue repair process. It is generally acknowledged that angiogenesis might contribute two both processes. In tumor growth, angiogenesis often increases oncogenic signaling, and in tissue repair, it decreases the stiffness of wound tissue and potentially exacerbates scar formation, resulting in pain and poor function. These poor outcomes are due to an increase in the expression of important genes involved in angiogenesis, such as hypoxia-inducible factor-1 alpha (HIF-1α) and its transcriptional target vascular endothelial growth factor (VEGF). Therefore, this adverse effect of angiogenesis should be taken into consideration. Limiting vessel growth instead of boosting growth may be beneficial for favorable long-term healing outcomes. Posttranslational modifications, including acetylation, which is mediated by histone acetyltransferases, and deacetylation, which is mediated by histone deacetylases (HDACs), are critical to HIF-1α function. Most studies have indicated that HDAC inhibitors (HDACIs) show great promise as antiangiogenic agents in the early phase of clinical trials. In this review, we discuss the role of the HDACs HIF-1α and VEGF in angiogenesis. Furthermore, we also discuss the molecular and cellular underpinnings of the effects of HDACIs on antiangiogenesis, which creates new avenues for anticancer therapeutics and the repair of wounded tissue.
Studies showed that energy metabolism plays a pivotal role in the differentiation of stem cells. Previous studies revealed that simulated microgravity (SMG) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs). However, the underlying relationship between osteogenesis and energy metabolism under SMG conditions is not fully understood. In the present study, we investigated mitochondrial oxidative phosphorylation (OXPHOS) by assessing the level of peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), mitochondrial DNA (mtDNA) copy number, mitochondrial mass and oxygen consumption rate (OCR) during osteogenesis of MSCs under SMG conditions. We found that SMG inhibited osteogenic differentiation and OXPHOS of MSCs. Moreover, the expression of sirtuin 1 (Sirt1), an important energy sensor, significantly decreased. After upregulating the expression of Sirt1 using resveratrol, an activator of Sirt1, SMG-inhibited OXPHOS and osteogenic differentiation of MSCs were recovered. Taken together, our results suggest that SMG suppresses osteogenic differentiation of MSCs by inhibiting OXPHOS, indicating that OXPHOS might serve as a potential therapeutic target for repairing bone loss under microgravity conditions.