Mechanotransduction is the process by which physical force is converted into a biochemical signal that is used in development and physiology; meanwhile, it is intended for the ability of cells to sense and respond to mechanical forces by activating intracellular signals transduction pathways and the relative phenotypic adaptation. It encompasses the role of mechanical stimuli for developmental, morphological characteristics, and biological processes in different organs; the response of cells to mechanically induced force is now also emerging as a major determinant of disease. Due to fluid shear stress caused by blood flowing tangentially across the lumen surface, cells of the cardiovascular system are typically exposed to a variety of mechanotransduction. In the body, tissues are continuously exposed to physical forces ranging from compression to strain, which is caused by fluid pressure and compressive forces. Only lately, though, has the importance of how forces shape stem cell differentiation into lineage-committed cells and how mechanical forces can cause or exacerbate disease besides organizing cells into tissues been acknowledged. Mesenchymal stem cells (MSCs) are potent mediators of cardiac repair which can secret a large array of soluble factors that have been shown to play a huge role in tissue repair. Differentiation of MSCs is required to regulate mechanical factors such as fluid shear stress, mechanical strain, and the rigidity of the extracellular matrix through various signaling pathways for their use in regenerative medicine. In the present review, we highlighted mechanical influences on the differentiation of MSCs and the general factors involved in MSCs differentiation. The purpose of this study is to demonstrate the progress that has been achieved in understanding how MSCs perceive and react to their mechanical environment, as well as to highlight areas where more research has been performed in previous studies to fill in the gaps.

Cardiac muscle cells have an innate capacity to perceive and react to mechanical strain via a mechanism known as mechanotransduction, whereby the cardiac muscle cells are intrinsically capable of sensing and responding to mechanical strain. This process occurs in the heart when mechanical inputs are converted to biochemical processes that result in myocardial structure and function changes. Mechanotransduction and its downstream effects work as compensatory mechanisms during early load adaptation. However, prolonged, and aberrant loading may cause maladaptive remodeling, resulting in altered physiological function, pathological cardiac hypertrophy, and heart failure. The rapid advancement of stem cell research has raised the hopes of both patients and clinicians. Mesenchymal progenitors have become one of the most intriguing possibilities for treating illnesses ranging from cartilage abnormalities to heart issues. Their immunomodulatory properties have also allowed for allogenic usage, besides expanding their potential for cardiomyocyte applications. In the present review, we highlighted mesenchymal stem cells (MSCs) in cardiovascular mechanotransduction, differentiation of cardiomyocytes and the use of MSCs in cardiovascular disease and tissue engineering.

Advances in cell-based regenerative therapy create new opportunities for the treatment of bone-related disorders and injuries, by improving the reparative phase of bone healing. Apart from the classical approach of bone grafting, the application of cell-based therapies, particularly stem cells (SCs), has gained a lot of attention in recent years. SCs play an important role in regenerative therapy due to their excellent ability to differentiate into bone-forming cells. Regeneration of new bone is regulated by a wide variety of signalling molecules and intracellular networks, which are responsible for coordinating cellular processes. The activated signalling cascade is significantly involved in cell survival, proliferation, apoptosis, and interaction with the microenvironment and other types of cells within the healing site. Despite the increasing evidence from studies conducted on signalling pathways associated with bone formation, the exact mechanism involved in controlling the differentiation stage of transplanted cells is not well understood. Identifying the key activated pathways involved in bone regeneration may allow for precise manipulation of the relevant signalling molecules within the progenitor cell population to accelerate the healing process. The in-depth knowledge of molecular mechanisms would be advantageous in improving the efficiency of personalised medicine and targeted therapy in regenerative medicine. In this review, we briefly introduce the theory of bone repair mechanism and bone tissue engineering followed by an overview of relevant signalling pathways that have been identified to play an important role in cell-based bone regenerative therapy.

Steadily rising population ageing is a global demographic trend due to the advancement of new treatments and technologies in the medical field. This trend also indicates an increasing prevalence of age-associated diseases, such as loss of muscle mass (sarcopenia), which tends to afflict the older population. The deterioration in muscle function can cause severe disability and seriously affects a patient’s quality of life. Currently, there is no treatment to prevent and reverse age-related skeletal muscle ageing frailty. Existing interventions mainly slow down and control the signs and symptoms. Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) therapy is a promising approach to attenuate age-related skeletal muscle ageing frailty. However, more studies, especially large-scale randomised clinical trials need to be done in order to determine the adequacy of MSC-EV therapy in treating age-related skeletal muscle ageing frailty. This review compiles the present knowledge of the causes and changes regarding skeletal muscle ageing frailty and the potential of MSC-EV transplantation as a regenerative therapy for age-related skeletal muscle ageing frailty and its clinical trials.

Background: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Method: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms. Results: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes—IFNE, PTCH2 and SEMA3D—which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes—ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117—harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway. Conclusion: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

This review provides an overview of the integrin signaling pathways and their roles in mesenchymal stem cell differentiation into adipocytes, chondrocytes, and osteoblasts. In these three differentiated cells, the cell extracellular matrix plays an important role in regulating the integrin signaling pathway, as the presence of growth factors and other molecules in the extracellular matrix will affect the cell differentiation. The focus of this review is to elucidate the role of the integrin signaling pathway in adipogenesis, chondrogenesis, and osteogenesis, highlighting its diverse contributions to tissue homeostasis and repair. By synthesizing current knowledge, this paper aims to inspire further research into the therapeutic potential of targeting integrin pathways in stem cell-based tissue engineering.