Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration.

The skin is made up of a plethora of cells arranged in multiple layers with complex and intricate vascular networks, creating a dynamic microenvironment of cells-to-matrix interactions. With limited donor sites, engineered skin substitute has been in high demand for many therapeutic purposes. Over the years, remarkable progress has occurred in the skin tissue-engineering field to develop skin grafts highly similar to native tissue. However, the major hurdle to successful engraftment is the incorporation of functional vasculature to provide essential nutrients and oxygen supply to the embedded cells. Limitations of traditional tissue engineering have driven the rapid development of vascularized skin tissue production, leading to new technologies such as 3D bioprinting, nano-fabrication and micro-patterning using hydrogel based-scaffold. In particular, the key hope to bioprinting would be the generation of interconnected functional vessels, coupled with the addition of specific cell types to mimic the biological and architectural complexity of the native skin environment. Additionally, stem cells have been gaining interest due to their highly regenerative potential and participation in wound healing. This review briefly summarizes the current cell therapies used in skin regeneration with a focus on the importance of vascularization and recent progress in 3D fabrication approaches to generate vascularized network in the skin tissue graft.

Mitochondria: A Potential Rejuvenation Tool against Aging.

Aging is a complex physiological process encompassing both physical and cognitive decline over time. This intricate process is governed by a multitude of hallmarks and pathways, which collectively contribute to the emergence of numerous age-related diseases. In response to the remarkable increase in human life expectancy, there has been a substantial rise in research focusing on the development of anti-aging therapies and pharmacological interventions. Mitochondrial dysfunction, a critical factor in the aging process, significantly impacts overall cellular health. In this extensive review, we will explore the contemporary landscape of anti-aging strategies, placing particular emphasis on the promising potential of mitotherapy as a ground-breaking approach to counteract the aging process. Moreover, we will investigate the successful application of mitochondrial transplantation in both animal models and clinical trials, emphasizing its translational potential. Finally, we will discuss the inherent challenges and future possibilities of mitotherapy within the realm of aging research and intervention.

Applications of miRNAs in cardiac development, disease progression and regeneration.

Development of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.

Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder that is commonly caused by the m.3243A > G mutation in the MT-TL1 gene encoding for mitochondrial tRNA(Leu(UUR)). While clinical studies reported cerebral infarcts, atherosclerotic lesions, and altered vasculature and stroke-like episodes (SLE) in MELAS patients, it remains unclear how this mutation causes the onset and subsequent progression of the disease. Here, we report that in addition to endothelial dysfunction, diseased endothelial cells (ECs) were found to be pro-atherogenic and pro-inflammation due to high levels of ROS and Ox-LDLs, and high basal expressions of VCAM-1, in particular isoform b, respectively. Consistently, more monocytes were found to adhere to MELAS ECs as compared to the isogenic control, suggesting the presence of an atherosclerosis-like pathology in MELAS. Notably, these disease phenotypes in endothelial cells can be effectively reversed by anti-oxidant treatment suggesting that the lowering of ROS is critical for treating patients with MELAS syndrome.