Journal of Stem Cell Research and Tissue Engineering

DECODING YAP-DRIVEN MALIGNANT REPROGRAMMING IN ORAL EPITHELIAL STEM CELLS THROUGH SINGLE-CELL ANALYSIS

Hanisa Aulia Maharani — 2025-05-30

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSC), is characterized by high mortality rates and cellular heterogeneity that complicates early detection and treatment. Recent advances in cancer biology suggest that tumorigenesis involves reprogramming of epithelial progenitor cells into cancer stem-like cells (CSCs), driven by oncogenic signaling such as Yes-associated protein (YAP) activation. YAP, a key effector of the Hippo pathway, regulates transcriptional programs involved in cell proliferation, dedifferentiation, and inhibition of differentiation. However, the specific mechanisms by which YAP reprograms oral epithelial stem cells remain incompletely understood. This literature review systematically explores findings from studies published between 2020 and 2025 that investigate the role of YAP in malignant reprogramming, particularly through single-cell analysis approaches. Articles were sourced from PubMed and Google Scholar using defined inclusion criteria, focusing on original studies involving in vitro, in vivo, or bioinformatic models. The review highlights that YAP activation in oral epithelial cells induces stemness-associated genes (e.g., SOX2, NANOG, OCT4), represses differentiation pathways (Notch, p63), and promotes epithelial-mesenchymal transition (EMT) markers (ZEB1, SNAI2, VIM). Single-cell RNA sequencing (scRNA-seq) has revealed dynamic and hybrid cell states, supporting the view that YAP-driven transformation is gradual and reversible. YAP also shapes the tumor microenvironment by inducing cytokines that recruit tumor-supportive immune and stromal cells. Key YAP-regulated targets such as CTGF, AXL, and ITGA6 emerge as potential therapeutic entry points, as their inhibition reduces proliferation and stemness. These findings underscore YAP’s central role in oral carcinogenesis and its promise as a molecular target for early intervention and therapy.

STEM CELL HIERARCHY AND IMMUNE TOLERANCE IN BONE MARROW MICHES: MECHANISMS AND EMERGING PERSPECTIVES

Harry Elyusaputra — 2025-05-30

Bone marrow niches play a crucial role in regulating the hierarchy of hematopoietic stem cells (HSCs) and immune tolerance. In this microenvironment, interactions between niche cells and molecular components such as Nitric Oxide (NO) and the CD200 protein influence HSC function. NO acts as a signaling molecule that supports HSC proliferation at low concentrations and promotes differentiation at higher concentrations. HSCs with high NO production are often located near CD200-rich capillaries, providing protection from immune responses. Additionally, the signaling pathway involving IFT20, CD200, eNOS, and autophagy supports cellular homeostasis and the survival of cells under stress, including in cancer. The expression of CD200 in capillaries contributes to a tolerogenic immune environment, protecting tissues from excessive inflammation. However, excessive CD200 expression can be exploited by tumor cells to evade immune detection. This review highlights the critical role of the bone marrow microenvironment in regulating stem cell behavior and immune tolerance, offering insights into how these molecular interactions govern stem cell fate and tissue homeostasis. A deeper understanding of these pathways can pave the way for novel therapeutic strategies in blood disorders, cancer, and inflammatory diseases. By unraveling the intricate molecular interactions within the bone marrow niche, this research provides new perspectives on stem cell regulation and immune tolerance, with implications for improving clinical outcomes in stem cell-based therapies.

MESENCHYMAL STEM CELLS FROM ADIPOSE TISSUE TO TIGHTEN FACIAL SKIN

Adilla Syahsiyatun Najah — 2025-05-30

Skin elasticity is an important aspects of facial care. This study aims to explore the potential of mesenchymal stem cells (MSCs) derived from adipose tissue (adipose-derived stem cells) in facial skin tightening and assess their advantages and limitations in clinical applications. The methods used include literature searches from various officially published online sources as well as analysis of research data regarding the process of isolation, culture, differentiation and clinical applications of ADSCs. The main findings show that adipose-derived stem cells (ADSCs) are able to form new collagen, increase skin elasticity, and repair tissue damage due to aging. The culture process involving isolation of cells from adipose tissue and differentiation of the cells into fibroblasts is essential to exploit the regenerative potential of these cells. Although this technology is promising, this study also identified technical and regulatory challenges that need to be overcome, including patient health criteria, safe ADSc harvest procedures, isolation and culture processes that have a high chance of differentiation and post-application care of ADSc therapy. The significance of these findings is that a better understanding of the mechanism of action of ADSCs can make a positive contribution to the development of beauty therapies that are more effective and safer compared to conventional methods that are often unsatisfactory. Additionally, this approach is expected to provide a long-term solution for individuals who wish to maintain a youthful appearance without the risk of significant side effects. Thus, this research can be a step in integrating stem cell technology in the beauty industry, especially for anti-aging treatments.

LONG-TERM EVALUATION OF THE SAFETY AND EFFECTIVENESS OF NEURAL STEM CELL TRANSPLANTATION FOR CHRONIC THORACIC SPINAL CORD INJURY

Hanisa Aulia Maharani — 2025-05-30

Spinal cord injury (SCI) is a debilitating neurological condition that leads to partial or complete loss of motor and sensory function, depending on the injury’s severity and location. Conventional therapies focus on surgical stabilization, prevention of secondary damage, and rehabilitation. However, these approaches often fall short in restoring long-term functionality. In recent years, cell-based therapies have emerged as promising alternatives, particularly those involving neural stem cells (NSCs). This literature review explores the long-term safety and effectiveness of NSC transplantation for chronic thoracic SCI, based on studies published between 2010 and 2025. Research shows that fetal-derived NSCs, such as HuCNS-SC, demonstrate a high safety profile and low risk of tumor formation due to their committed neural lineage. Clinical trials report early signs of motor improvement and reduced spasticity in chronic SCI patients following transplantation. Additionally, mesenchymal stem cells (MSCs) have shown the ability to migrate to injury sites and exert therapeutic effects, though these benefits tend to be short-lived. The post-injury inflammatory microenvironment poses a significant barrier to the success of NSC therapies by impairing stem cell differentiation and survival. Therefore, immunosuppressive regimens are often employed to enhance NSC efficacy by creating a more supportive environment. Overall, while both NSCs and MSCs offer promising avenues for SCI treatment, long-term recovery likely requires multimodal approaches that address both neural regeneration and immune modulation. Continued research is essential to optimize these therapies and translate them into effective clinical treatments for patients with chronic SCI.

FUNCTIONAL ROLE OF VIMENTIN'S CYSTEINE IN XIST-MEDIATED EMT INHIBITION IN BREAST CANCER

Jayanti — 2025-05-30

Breast cancer is the most commonly diagnosed malignancy among women worldwide and a leading cause of cancer-related mortality, primarily due to its high metastatic potential. One mechanism underlying metastasis is the epithelial-to-mesenchymal transition (EMT), which enhances cancer cell mobility, invasiveness, and resistance to treatment. Vimentin, a type III intermediate filament protein, is a hallmark of EMT and plays a structural and regulatory role in cytoskeletal organization and cellular stress responses. Recent studies have highlighted the importance of a single cysteine residue at position 328 (C328) in vimentin, which functions as a redox-sensitive site influencing filament dynamics. However, the role of C328 in cancer progression remained largely unexplored. This literature review investigates the effect of a single amino acid substitution—C328 to serine (C328S)—on breast cancer cell behavior, focusing on findings published between 2020 and 2025, sourced from PubMed and Google Scholar. Evidence from MCF-7 breast cancer cell models reveals that expression of C328S-VIM induces morphological changes, cytoskeletal disorganization, and increased proliferation, migration, and invasion. Notably, C328S-VIM upregulates the long non-coding RNA XIST, which promotes EMT, estrogen independence, and stem-like properties. These findings indicate that the native C328 residue serves a tumor-suppressive function, partly through modulation of XIST activity. Overall, this review presents a novel insight into how a single amino acid mutation in vimentin can reprogram breast cancer cells toward a more aggressive and stem-like phenotype. The study highlights C328 as a potential therapeutic target and broadens our understanding of the molecular mechanisms driving breast cancer progression.