Current stem cell research & therapy最新文献

Stem cells, which were initially identified in the 1900s, are distinct cells with the potential to replenish themselves as well as differentiate into specialised cells with certain forms and functions. Cancer stem cells play a significant role in the growth and recurrence of the tumours and, similar to normal stem cells, are capable of proliferating and differentiating. Traditional cancer treatments are ineffective against cancer stem cells, which leads to tumour regrowth. Cancer stem cells are thought to emerge as a result of epithelial-to-mesenchymal transition pathways. Brain, prostate, pancreatic, blood, ovarian, lung, liver, melanomas, AML, and breast cancer stem cells are among the most prevalent cancer forms. This review aims to comprehend the possibility of using specific forms of nanotechnology to replace cancer stem cells. In terms of nanotechnology, magnetic nanoparticles can deliver medications, especially to the target region without harming healthy cells, and they are biocompatible. In order to kill glioma cancer stem cells, the gold nanoparticles bond with DNA and function as radio sensitizers. In contrast, liposomes can circulate and traverse biological membranes and exhibit high therapeutic efficacy, precise targeting, and better drug release. Similar to carbon nanotubes, grapheme, and grapheme oxide, these substances can be delivered specifically when utilized in photothermal therapy. Recent treatments including signaling pathways and indicators targeted by nanoparticles are being researched. Future research in nanotechnology aims to develop more effective and targeted medicinal approaches. The results of the current investigation also showed that this technology's utilization will improve medical therapy and treatment.

Acute radiation syndrome (ARS) is also known as triple syndrome, which develops after whole-body radiation exposure. During unforeseen exposures, these syndromes are set in depending on the dose of radiation. Cell-based therapy, especially using stem cells and their soluble factors, is gaining wide attention in the field of regenerative medicine to treat various diseases, including degenerative diseases. Stem cells attract prime attention because of their profound inherent tissue repair capability and regeneration potential. Further, stem cell therapy can be one of the promising strategies for the amelioration of ARS because of its ability to lodge in damaged tissue and release regenerative cytokines by sensing the local injury. In this regard, human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) have gained substantial attention for their applications in the treatment of various human diseases due to several advantages offered by them. This article is intended to provide future perspective on the use of WJ-MSCs for the management of accidental radiation injury in pre-clinical models, and finally, their utility in regeneration of damaged tissues and organs.

Introduction: Extracellular vesicles (EVs) are one of the crucial means of intercellular communication, which takes many different forms. They are heterogeneous, secreted by a range of cell types, and can be generally classified into microvesicles and exosomes depending on their location and function. Exosomes are small EVs with diameters of about 30-150 nm and diverse cell sources.

Methods: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of recent years, using the search string "Exosome" and "Neurodegenerative diseases."

Results: The exosomes have attracted interest as a significant biomarker for a better understanding of disease development, gene silencing delivery, and alternatives to stem cell-based therapy because of their low-invasive therapeutic approach, repeatable distribution in the central nervous system (CNS), and high efficiency. Also, they are nanovesicles that carry various substances, which can have an impact on neural plasticity and cognitive functioning in both healthy and pathological circumstances. Therefore, exosomes are conceived as nanovesicles containing proteins, lipids, and nucleic acids. However, their composition varies considerably depending on the cells from which they are produced.

Conclusion: In the present review, we discuss several techniques for the isolation of exosomes from different cell sources. Furthermore, reviewing research on exosomes' possible functions as carriers of bioactive substances implicated in the etiology of neurodegenerative illnesses, we further examine them. We also analyze the preclinical and clinical research that shows exosomes to have therapeutic potential.

Background: The unique potential of stem cells to restore vision and regenerate damaged ocular cells has led to the increased attraction of researchers and ophthalmologists to ocular regenerative medicine in recent decades. In addition, advantages such as easy access to ocular tissues, non-invasive follow-up, and ocular immunologic privilege have enhanced the desire to develop ocular regenerative medicine.

Objective: This study aimed to characterize central and nasal orbital adipose stem cells (OASCs) and their neural differentiation potential.

Methods: The central and nasal orbital adipose tissues extracted during an upper blepharoplasty surgery were explant-cultured in Dulbecco's Modified Eagle Medium (DMEM)/F12 supplemented with 10% fetal bovine serum (FBS). Cells from passage 3 were characterized morphologically by osteogenic and adipogenic differentiation potential and by flow cytometry for expression of mesenchymal (CD73, CD90, and CD105) and hematopoietic (CD34 and CD45) markers. The potential of OASCs for the expression of NGF, PI3K, and MAPK and to induce neurogenesis was assessed by real-time PCR.

Results: OASCs were spindle-shaped and positive for adipogenic and osteogenic induction. They were also positive for mesenchymal and negative for hematopoietic markers. They were positive for NGF expression in the absence of any significant alteration in the expression of PI3K and MAPK genes. Nasal OASCs had higher expression of CD90, higher potential for adipogenesis, a higher level of NGF expression under serum-free supplementation, and more potential for neuron-like morphology.

Conclusion: We suggested the explant method of culture as an easy and suitable method for the expansion of OASCs. Our findings denote mesenchymal properties of both central and nasal OASCs, while mesenchymal and neural characteristics were expressed stronger in nasal OASCs when compared to central ones. These findings can be added to the literature when cell transplantation is targeted in the treatment of neuro-retinal degenerative disorders.

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.

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.

Diabetes is a complex metabolic disease with a high global prevalence. The health and quality of life of patients with diabetes are threatened by many complications, including diabetic foot ulcers, diabetic kidney diseases, diabetic retinopathy, and diabetic peripheral neuropathy. The application of mesenchymal stem/stromal cells (MSCs) in cell therapies has been recognized as a potential treatment for diabetes and its complications. MSCs were originally thought to exert biological effects exclusively by differentiating and replacing specific impaired cells. However, the paracrine function of factors secreted by MSCs may exert additional protective effects. MSCs secrete multiple compounds, including proteins, such as growth factors, chemokines, and other cytokines; nucleic acids, such as miRNAs; and lipids, extracellular vesicles (EVs), and exosomes (Exos). Collectively, these secreted compounds are called the MSC secretome, and usage of these chemicals in cell-free therapies may provide stronger effects with greater safety and convenience. Recent studies have demonstrated positive effects of the MSC secretome, including improved insulin sensitivity, reduced inflammation, decreased endoplasmic reticulum stress, enhanced M2 polarization of macrophages, and increased angiogenesis and autophagy; however, the mechanisms leading to these effects are not fully understood. This review summarizes the current research regarding the secretome derived from MSCs, including efforts to quantify effectiveness and uncover potential molecular mechanisms in the treatment of diabetes and related disorders. In addition, limitations and challenges are also discussed so as to facilitate applications of the MSC secretome as a cell-free therapy for diabetes and its complications.

Chronic liver disease is a known risk factor for the development of liver cancer, and the development of microRNA (miRNA) liver therapies has been hampered by the difficulty of delivering miRNA to damaged tissues. In recent years, numerous studies have shown that hepatic stellate cell (HSC) autophagy and exosomes play an important role in maintaining liver homeostasis and ameliorating liver fibrosis. In addition, the interaction between HSC autophagy and exosomes also affects the progression of liver fibrosis. In this paper, we review the research progress of mesenchymal stem cell-derived exosomes (MSC-EVs) loaded with specific miRNA and autophagy, and their related signaling pathways in liver fibrosis, which will provide a more reliable basis for the use of MSC-EVs for therapeutic delivery of miRNAs targeting the chronic liver disease.

Ischemic stroke is the leading cause of death and disability worldwide, with increasing incidence and mortality, imposing a significant social and economic burden on patients and their families. However, cerebral vascular occlusion leads to acute loss of neurons and destruction of synaptic structures. The limited treatment options cannot adequately address intra-neuronal mitochondrial dysfunction due to stroke. Therefore, stem cell-derived mitochondria transplantation plays an important role in neuronal protection and recovery after stroke, when combined with the intracranial and extracranial immunoregulatory effects of stem cell therapy, revealing the mechanism of transferred mitochondria in stem cells in protecting neurological function among chronic-phase ischemic stroke by affecting the endogenous apoptotic pathway of neuronal cells. This research elaborated on the mitochondrial dysfunction in neurons after ischemic stroke, followed by human bone marrow mesenchymal stem cells (hBMSC) rescued damaged neurons by mitochondrial transfer through tunneling nanotubes (TNTs), and the immunomodulatory effect of the preferential transfer of stem cells to the spleen when transplanted into the body.which created an immune environment for nerve repair, as well as improved neurological recovery after the chronic phase of stroke. This review is expected to provide a novel idea for applying intracranial stem cell transplantation in chronic-phase ischemic stroke treatment.

Aim: This study aimed to identify the molecular type and prognostic model of lung adenocarcinoma (LUAD) based on cancer stem cell-related genes. Studies have shown that cancer stem cells (CSC) are involved in the development, recurrence, metastasis, and drug resistance of tumors.

Method: The clinical information and RNA-seq of LUAD were obtained from the TCGA database. scRNA dataset GSE131907 and 5 GSE datasets were downloaded from the GEO database. Molecular subtypes were identified by ConsensusClusterPlus. A CSC-related prognostic signature was then constructed via univariate Cox and LASSO Cox-regression analysis.

Result: A scRNA-seq GSE131907 dataset was employed to obtain 11 cell clusters, among which, 173 differentially expressed genes in CSC were identified. Moreover, the CSC score and mRNAsi were higher in tumor samples. 18 of 173 genes were survival time-associated genes in both the TCGA-LUDA dataset and the GSE dataset. Next, two molecular subtypes (namely, CSC1 and CSC2) were identified based on 18 survival-related CSC genes with distinct immune profiles and noticeably different prognoses as well as differences in the sensitivity of chemotherapy drugs. 8 genes were used to build a prognostic model in the TCGA-LUAD dataset. High-risk patients faced worse survival than those with a low risk. The robust predictive ability of the risk score was validated by the time-dependent ROC curve revealed as well as the GSE dataset. TIDE analysis showed a higher sensitivity of patients in the low group to immunotherapy.

Conclusion: This study has revealed the effect of CSC on the heterogeneity of LUAD, and created an 8 genes prognosis model that can be potentially valuable for predicting the prognosis of LUAD and response to immunotherapy.