Current Stem Cell Research & Therapy - Volume 19, Issue 3, 2024

Treating chronic wounds is a common and costly challenge worldwide. More advanced treatments are needed to improve wound healing and prevent severe complications such as infection and amputation. Like other medical fields, there have been advances in new technologies promoting wound healing potential.Regenerative medicine as a new method has aroused hope in treating chronic wounds. The technology improving wound healing includes using customizable matrices based on synthetic and natural polymers, different types of autologous and allogeneic cells at different differentiation phases, small molecules, peptides, and proteins as a growth factor, RNA interference, and gene therapy. In the last decade, various types of wound dressings have been designed. Emerging dressings include a variety of interactive/ bioactive dressings and tissue-engineering skin options. However, there is still no suitable and effective dressing to treat all chronic wounds.This article reviews different wounds and common treatments, advanced technologies and wound dressings, the advanced wound care market, and some interactive/bioactive wound dressings in the market.

Severe corneal disorders due to infective aetiologies, trauma, chemical injuries, and chronic cicatricial inflammations, are among vision-threatening pathologies leading to permanent corneal scarring. The whole cornea or lamellar corneal transplantation is often used as a last resort to restore vision. However, limited autologous tissue sources and potential adverse post-allotransplantation sequalae urge the need for more robust and strategic alternatives. Contemporary management using cultivated corneal epithelial transplantation has paved the way for utilizing stem cells as a regenerative potential. Humaninduced pluripotent stem cells (hiPSCs) can generate ectodermal progenitors and potentially be used for ocular surface regeneration. This review summarizes the process of corneal morphogenesis and the signaling pathways underlying the development of corneal epithelium, which is key to translating the maturation and differentiation process of hiPSCs in vitro. The current state of knowledge and methodology for driving efficient corneal epithelial cell differentiation from pluripotent stem cells are highlighted.

Genome editing has enhanced our ability to understand the role of genetics in a number of diseases by facilitating the development of more precise cellular and animal models to study pathophysiological processes. These advances have shown extraordinary promise in a multitude of areas, from basic research to applied bioengineering and biomedical research. Induced pluripotent stem cells (iPSCs) are known for their high replicative capacity and are excellent targets for genetic manipulation as they can be clonally expanded from a single cell without compromising their pluripotency. Clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR/Cas RNA-guided nucleases have rapidly become the method of choice for gene editing due to their high specificity, simplicity, low cost, and versatility. Coupling the cellular versatility of iPSCs differentiation with CRISPR/Cas9-mediated genome editing technology can be an effective experimental technique for providing new insights into the therapeutic use of this technology. However, before using these techniques for gene therapy, their therapeutic safety and efficacy following models need to be assessed. In this review, we cover the remarkable progress that has been made in the use of genome editing tools in iPSCs, their applications in disease research and gene therapy as well as the hurdles that remain in the actual implementation of CRISPR/Cas systems.

With the development of society, the global population is showing a trend of aging. It is well known that age is one of the factors affecting wound healing. Aging compromises the normal physiological process of wound healing, such as the change of skin structure, the decrease of growth factors, the deceleration of cell proliferation, and the weakening of migration ability, hence delaying wound healing. At present, research in adult stem cell-related technology and its derived regenerative medicine provides a novel idea for the treatment of senile wounds. Studies have confirmed that CD271 (P75 neurotropism receptor/P75NTR)-positive cells (CD271⁺ cells) are a kind of stem cells with a stronger ability of proliferation, differentiation, migration and secretion than CD271 negative (CD271^- cells). Meanwhile, the total amount and distribution of CD271 positive cells in different ages of skin are also different, which may be related to the delayed wound healing of aging skin. Therefore, this article reviews the relationship between CD271⁺ cells and senile wounds and discusses a new scheme for the treatment of senile wounds.

There has been a lot of interest in stem cell therapy as a means of curing disease in recent years. Despite extensive usage of stem cell therapy in the treatment of a wide range of medical diseases, it has been hypothesized that it plays a key part in the progression of cancer. Breast cancer is still the most frequent malignancy in women globally. However, the latest treatments, such as stem cell targeted therapy, are considered to be more effective in preventing recurrence, metastasis, and chemoresistance of breast cancer than older methods like chemotherapy and radiation. This review discusses the characteristics of stem cells and how stem cells may be used to treat breast cancer.

Senescence refers to the irreversible state in which cells enter cell cycle arrest due to internal or external stimuli. The accumulation of senescent cells can lead to many age-related diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancers. MicroRNAs are short non-coding RNAs that bind to target mRNA to regulate gene expression after transcription and play an important regulatory role in the aging process. From nematodes to humans, a variety of miRNAs have been confirmed to alter and affect the aging process. Studying the regulatory mechanisms of miRNAs in aging can further deepen our understanding of cell and body aging and provide a new perspective for the diagnosis and treatment of aging-related diseases. In this review, we illustrate the current research status of miRNAs in aging and discuss the possible prospects for clinical applications of targeting miRNAs in senile diseases.

Exosomes are extracellular vesicles (EVs) that originate from endocytic membranes. The transfer of biomolecules and biological compounds such as enzymes, proteins, RNA, lipids, and cellular waste disposal through exosomes plays an essential function in cell-cell communication and regulation of pathological and physiological processes in skin disease. The skin is one of the vital organs that makes up about 8% of the total body mass. This organ consists of three layers, epidermis, dermis, and hypodermis that cover the outer surface of the body. Heterogeneity and endogeneity of exosomes is an advantage that distinguishes them from nanoparticles and liposomes and leads to their widespread usage in the remedy of dermal diseases. The biocompatible nature of these extracellular vesicles has attracted the attention of many health researchers. In this review article, we will first discuss the biogenesis of exosomes, their contents, separation methods, and the advantages and disadvantages of exosomes. Then we will highlight recent developments related to the therapeutic applications of exosomes in the treatment of common skin disorders like atopic dermatitis, alopecia, epidermolysis bullosa, keloid, melanoma, psoriasis, and systemic sclerosis.

A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor 4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming mechanisms are still poorly understood medically. This technique has dramatically improved performance and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine. Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds, impacts kinetics, quality, and efficiency in stem cell research.

Background: This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats.Methods: Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot.Result: Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins.Conclusion: Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.

Background: Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC.Methods: Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets.Results: LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses.Conclusion: The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.

Objectives: Periodontal ligament stem cells (PDLSCs) are ideal seed cells for periodontal tissue regeneration. Our previous studies have indicated that the histone methyltransferase PRDM9 plays an important role in human periodontal ligament stem cells (hPDLSCs). Whether FBLN5, which is a downstream gene of PRDM9, also has a potential impact on hPDLSCs is still unclear.Methods: Senescence was assessed using β-galactosidase and Enzyme-linked immunosorbent assay (ELISA). Osteogenic differentiation potential of hPDLSCs was measured through Alkaline phosphatase (ALP) activity assay and Alizarin red detection, while gene expression levels were evaluated using western blot and RT-qPCR analysis.Results: FBLN5 overexpression promoted the osteogenic differentiation and senescence of hPDLSCs. FBLN5 knockdown inhibited the osteogenic differentiation and senescence of hPDLSCs. Knockdown of PRDM9 decreased the expression of FBLN5 in hPDLSCs and inhibited senescence of hPDLSCs. Additionally, both FBLN5 and PRDM9 promoted the expression of phosphorylated p38 MAPK, Erk1/2 and JNK. The p38 MAPK pathway inhibitor SB203580 and the Erk1/2 pathway inhibitor PD98059 have the same effects on inhibiting the osteogenic differentiation and senescence of hPDLSCs. The JNK pathway inhibitor SP600125 reduced the senescence of hPDLSCs.Conclusion: FBLN5 promoted senescence and osteogenic differentiation of hPDLSCs via activation of the MAPK signaling pathway. FBLN5 was positively targeted by PRDM9, which also activated the MAPK signaling pathway.