RESUMEN
Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs.
RESUMEN
The oviduct provides an optimal environment for the final preparation, transport, and survival of gametes, the fertilization process, and early embryonic development. Most of the studies on reproduction are based on in vitro cell culture models because of the cell's accessibility. It creates opportunities to explore the complexity of directly linked processes between cells. Previous studies showed a significant expression of genes responsible for cell differentiation, maturation, and development during long-term porcine oviduct epithelial cells (POECs) in vitro culture. This study aimed at establishing the transcriptomic profile and comprehensive characteristics of porcine oviduct epithelial cell in vitro cultures, to compare changes in gene expression over time and deliver information about the expression pattern of genes highlighted in specific GO groups. The oviduct cells were collected after 7, 15, and 30 days of in vitro cultivation. The transcriptomic profile of gene expression was compared to the control group (cells collected after the first day). The expression of COL1A2 and LOX was enhanced, while FGFBP1, SERPINB2, and OVGP1 were downregulated at all selected intervals of cell culture in comparison to the 24-h control (p-value < 0.05). Adding new detailed information to the reproductive biology field about the diversified transcriptome profile in POECs may create new future possibilities in infertility treatments, including assisted reproductive technique (ART) programmes, and may be a valuable tool to investigate the potential role of oviduct cells in post-ovulation events.
Asunto(s)
Células Epiteliales , Transcriptoma , Animales , Femenino , Porcinos , Células Epiteliales/metabolismo , Células Epiteliales/citología , Perfilación de la Expresión Génica , Células Cultivadas , Oviductos/metabolismo , Oviductos/citología , Técnicas de Cultivo de Célula/métodos , Regulación de la Expresión Génica , Trompas Uterinas/metabolismo , Trompas Uterinas/citologíaRESUMEN
Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
Asunto(s)
Pulpa Dental , Medicina Regenerativa , Células Madre , Humanos , Pulpa Dental/citología , Medicina Regenerativa/métodos , Células Madre/citología , Células Madre/metabolismo , Animales , Diferenciación Celular , Trasplante de Células Madre/métodos , ARN no Traducido/genéticaRESUMEN
As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with age-related diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.
RESUMEN
Biomimetic scaffolds imitate native tissue and can take a multidimensional form. They are biocompatible and can influence cellular metabolism, making them attractive bioengineering platforms. The use of biomimetic scaffolds adds complexity to traditional cell cultivation methods. The most commonly used technique involves cultivating cells on a flat surface in a two-dimensional format due to its simplicity. A three-dimensional (3D) format can provide a microenvironment for surrounding cells. There are two main techniques for obtaining 3D structures based on the presence of scaffolding. Scaffold-free techniques consist of spheroid technologies. Meanwhile, scaffold techniques contain organoids and all constructs that use various types of scaffolds, ranging from decellularized extracellular matrix (dECM) through hydrogels that are one of the most extensively studied forms of potential scaffolds for 3D culture up to 4D bioprinted biomaterials. 3D bioprinting is one of the most important techniques used to create biomimetic scaffolds. The versatility of this technique allows the use of many different types of inks, mainly hydrogels, as well as cells and inorganic substances. Increasing amounts of data provide evidence of vast potential of biomimetic scaffolds usage in tissue engineering and personalized medicine, with the main area of potential application being the regeneration of skin and musculoskeletal systems. Recent papers also indicate increasing amounts of in vivo tests of products based on biomimetic scaffolds, which further strengthen the importance of this branch of tissue engineering and emphasize the need for extensive research to provide safe for humansbiomimetic tissues and organs. In this review article, we provide a review of the recent advancements in the field of biomimetic scaffolds preceded by an overview of cell culture technologies that led to the development of biomimetic scaffold techniques as the most complex type of cell culture.
RESUMEN
Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic.
RESUMEN
A disturbance of the structure of the aortic wall results in the formation of aortic aneurysm, which is characterized by a significant bulge on the vessel surface that may have consequences, such as distention and finally rupture. Abdominal aortic aneurysm (AAA) is a major pathological condition because it affects approximately 8% of elderly men and 1.5% of elderly women. The pathogenesis of AAA involves multiple interlocking mechanisms, including inflammation, immune cell activation, protein degradation and cellular malalignments. The expression of inflammatory factors, such as cytokines and chemokines, induce the infiltration of inflammatory cells into the wall of the aorta, including macrophages, natural killer cells (NK cells) and T and B lymphocytes. Protein degradation occurs with a high expression not only of matrix metalloproteinases (MMPs) but also of neutrophil gelatinase-associated lipocalin (NGAL), interferon gamma (IFN-γ) and chymases. The loss of extracellular matrix (ECM) due to cell apoptosis and phenotype switching reduces tissue density and may contribute to AAA. It is important to consider the key mechanisms of initiating and promoting AAA to achieve better preventative and therapeutic outcomes.
Asunto(s)
Aneurisma de la Aorta Abdominal , Masculino , Humanos , Femenino , Anciano , Aneurisma de la Aorta Abdominal/metabolismo , Aorta/metabolismo , Citocinas/metabolismo , Fenotipo , Apoptosis/genéticaRESUMEN
Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.
Asunto(s)
Transición Epitelial-Mesenquimal , Células Neoplásicas Circulantes , Células Madre Neoplásicas , Neovascularización Patológica , Humanos , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Neovascularización Patológica/patología , Neoplasias/patología , Neoplasias/metabolismo , Animales , Fenotipo , Proliferación Celular/genética , Células Madre/metabolismo , Células Madre/citología , Células Madre/patologíaRESUMEN
Ischemic stroke, which occurs due to the occlusion of cerebral arteries, is a common type of stroke. Recent research has highlighted the important role of long non-coding RNAs (lncRNAs) in the development of cerebrovascular diseases, specifically ischemic stroke. Understanding the functional roles of lncRNAs in ischemic stroke is crucial, given their potential contribution to the disease pathology. One noteworthy lncRNA is X-inactive specific transcript (XIST), which exhibits downregulation during the early stages of ischemic stroke and subsequent upregulation in later stages. XIST exert its influence on the development of ischemic stroke through interactions with multiple miRNAs and transcription factors. These interactions play a significant role in the pathogenesis of the condition. In this review, we have provided a comprehensive summary of the functional roles of XIST in ischemic stroke. By investigating the involvement of XIST in the disease process, we aim to enhance our understanding of the mechanisms underlying ischemic stroke and potentially identify novel therapeutic targets.
RESUMEN
It is now widely recognized that mesenchymal stem cells (MSCs) possess the capacity to differentiate into a wide array of cell types. Numerous studies have identified the role of lncRNA in the regulation of MSC differentiation. It is important to elucidate the role and interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of signalling pathways that govern MSC function. Furthermore, miRNAs and lncRNAs are important clinical for innovative strategies aimed at addressing a wide spectrum of existing and emerging disease. Hence it is important to consider their impact on MSC function and differentiation. Examining the data available in public databases, we have collected the literature containing the latest discoveries pertaining to human stem cells and their potential in both fundamental research and clinical applications. Furthermore, we have compiled completed clinical studies that revolve around the application of MSCs, shedding light on the opportunities presented by harnessing the regulatory potential of miRNAs and lncRNAs. This exploration of the therapeutic possibilities offered by miRNAs and lncRNAs within MSCs unveils exciting prospects for the development of precision therapies and personalized treatment approaches. Ultimately, these advancements promise to augment the efficacy of regenerative strategies and produce positive outcomes for patients. As research in this field continues to evolve, it is imperative to explore and exploit the vast potential of miRNAs and lncRNAs as therapeutic agents. The findings provide a solid basis for ongoing investigations, fuelling the quest to fully unlock the regenerative potential of MSCs.
Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismoRESUMEN
In vitro meat production presents a potential viable alternative for meat consumption, which could provide the consumer with a product indistinguishable from the original, with very similar nutritional and culinary values. Indeed, the alternative products currently accessible often lack comparable nutritional value or culinary attributes to their animal-derived counterparts. This creates challenges for their global acceptance, particularly in countries where meat consumption holds cultural significance. However, while cultured meat research has been progressing rapidly in recent years, some significant obstacles still need to be overcome before its possible commercialization. Hence, this review summarizes the most current knowledge regarding the history of cultured meat, the currently used cell sources and methods used for the purpose of in vitro meat production, with particular focus on the role of bioreactors, scaffolds and microcarriers in overcoming the current obstacles. The authors put the potential microcarrier and scaffold-based solutions in a context, discussing the ways in which they can impact the way forward for the technology, including the use of considering the potential practical and societal barriers to implementing it as a viable food source worldwide.
RESUMEN
Healing of dense regular connective tissue, due to a high fiber-to-cell ratio and low metabolic activity and regeneration potential, frequently requires surgical implantation or reconstruction with high risk of reinjury. An alternative to synthetic implants is using bioscaffolds obtained through decellularization, a process where the aim is to extract cells from the tissue while preserving the tissue-specific native molecular structure of the ECM. Proteins, lipids, nucleic acids and other various extracellular molecules are largely involved in differentiation, proliferation, vascularization and collagen fibers deposit, making them the crucial processes in tissue regeneration. Because of the multiple possible forms of cell extraction, there is no standardized protocol in dense regular connective tissue (DRCT). Many modifications of the structure, shape and composition of the bioscaffold have also been described to improve the therapeutic result following the implantation of decellularized connective tissue. The available data provide a valuable source of crucial information. However, the wide spectrum of decellularization makes it important to understand the key aspects of bioscaffolds relative to their potential use in tissue regeneration.
Asunto(s)
Ácidos Nucleicos , Medicina Regenerativa , Humanos , Diferenciación Celular , Implantación del Embrión , Neovascularización PatológicaRESUMEN
Small extracellular vesicles (sEVs) are a type of membranous vesicles that can be released by cells into the extracellular space. The relationship between sEVs and non-coding RNAs (ncRNAs) is highly intricate and interdependent. This symbiotic relationship plays a pivotal role in facilitating intercellular communication and holds profound implications for a myriad of biological processes. The concept of sEVs and their ncRNA cargo as a "Trojan Horse" highlights their remarkable capacity to traverse biological barriers and surreptitiously deliver their cargo to target cells, evading detection by the host-immune system. Accumulating evidence suggests that sEVs may be harnessed as carriers to ferry therapeutic ncRNAs capable of selectively silencing disease-driving genes, particularly in conditions such as cancer. This approach presents several advantages over conventional drug delivery methods, opening up new possibilities for targeted therapy and improved treatment outcomes. However, the utilization of sEVs and ncRNAs as therapeutic agents raises valid concerns regarding the possibility of unforeseen consequences and unintended impacts that may emerge from their application. It is important to consider the fundamental attributes of sEVs and ncRNAs, including by an in-depth analysis of the practical and clinical potentials of exosomes, serving as a representative model for sEVs encapsulating ncRNAs.
RESUMEN
BACKGROUND: Cell cycle regulation influences the proliferation of granulosa cells and affects many processes related to ovarian folliclular growth and ovulation. Abnormal regulation of the cell cycle can lead to many diseases within the ovary. The aim of this study was to describe the expression profile of genes within granulosa cells, which are related to the formation of the cytoskeleton, organization of cell organelles inside the cell, and regulation of cell division. Established in vitro primary cultures from porcine ovarian follicle granulosa cells were maintained for 48, 96, 144 h and evaluated via microarray expression analysis. RESULTS: Analyzed genes were assigned to 12 gene ontology groups "actin cytoskeleton organization", "actin filament organization", "actin filament-based process", "cell-matrix adhesion", "cell-substrate adhesion", "chromosome segregation", "chromosome separation", "cytoskeleton organization", "DNA integrity checkpoint", "DNA replication initiation", "organelle fision", "organelle organization". Among the genes with significantly changed expression, those whose role in processes within the ovary are selected for consideration. Genes with increased expression include (ITGA11, CNN1, CCl2, TPM2, ACTN1, VCAM-1, COL3A1, GSN, FRMD6, PLK2). Genes with reduced expression inlcude (KIF14, TACC3, ESPL1, CDC45, TTK, CDC20, CDK1, FBXO5, NEK2-NIMA, CCNE2). For the results obtained by microarray expressions, quantitative validation by RT-qPCR was performed. CONCLUSIONS: The results indicated expression profile of genes, which can be considered as new molecular markers of cellular processes involved in signaling, cell structure organization. The expression profile of selected genes brings new insight into regulation of physiological processes in porcine follicular granulosa cells during primary in vitro culture.
RESUMEN
Wharton's jelly (WJ) contains mesenchymal stem cells (MSCs) exhibiting broad immunomodulatory properties and differentiation capacity, which makes them a promising tool for cellular therapies. Although the osteogenic, chondrogenic and adipogenic differentiation is a gold standard for proper identification of MSCs, it is important to elucidate the exact molecular mechanisms governing these processes to develop safe and efficient cellular therapies. Umbilical cords were collected from healthy, full-term deliveries, for subsequent MSCs (WJ-MSCs) isolation. WJ-MSCs were cultivated in vitro for osteogenic, chondrogenic, adipogenic and neurogenic differentiation. The RNA samples were isolated and the transcript levels were evaluated using NovaSeq platform, which led to the identification of differentially expressed genes. Expression of H19 and SLPI was enhanced in adipocytes, chondrocytes and osteoblasts, and NPPB was decreased in all analyzed groups compared to the control. KISS1 was down-regulated in adipocytes, chondrocytes, and neural-like cells compared to the control. The most of identified genes were already implicated in differentiation of MSCs; however, some genes (PROK1, OCA2) have not yet been associated with initiating final cell fate. The current results indicate that both osteo- and adipo-induced WJ-MSCs share many similarities regarding the most overexpressed genes, while the neuro-induced WJ-MSCs are quite distinctive from the other three groups. Overall, this study provides an insight into the transcriptomic changes occurring during the differentiation of WJ-MSCs and enables the identification of novel markers involved in this process, which may serve as a reference for further research exploring the role of these genes in physiology of WJ-MSCs and in regenerative medicine.
Asunto(s)
Hormonas Gastrointestinales , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina , Gelatina de Wharton , Humanos , Condrocitos , Adipocitos , Diferenciación Celular/genética , Osteoblastos , Factores InmunológicosRESUMEN
Exosomal regulation is intimately involved in key cellular processes, such as migration, proliferation, and adhesion. By participating in the regulation of basic mechanisms, extracellular vesicles are important in intercellular signaling and the functioning of the mammalian reproductive system. The complexity of intercellular interactions in the ovarian follicle is also based on multilevel intercellular signaling, including the mechanisms involving cadherins, integrins, and the extracellular matrix. The processes in the ovary leading to the formation of a fertilization-ready oocyte are extremely complex at the molecular level and depend on the oocyte's ongoing relationship with granulosa cells. An analysis of gene expression from material obtained from a primary in vitro culture of porcine granulosa cells was employed using microarray technology. Genes with the highest expression (LIPG, HSD3B1, CLIP4, LOX, ANKRD1, FMOD, SHAS2, TAGLN, ITGA8, MXRA5, and NEXN) and the lowest expression levels (DAPL1, HSD17B1, SNX31, FST, NEBL, CXCL10, RGS2, MAL2, IHH, and TRIB2) were selected for further analysis. The gene expression results obtained from the microarrays were validated using quantitative RT-qPCR. Exosomes may play important roles regarding intercellular signaling between granulosa cells. Therefore, exosomes may have significant applications in regenerative medicine, targeted therapy, and assisted reproduction technologies.
Asunto(s)
Células de la Granulosa , Folículo Ovárico , Femenino , Porcinos , Animales , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , Oocitos/metabolismo , Ovario/metabolismo , Proliferación Celular/genética , MamíferosRESUMEN
Heart failure remains a major cause of death worldwide. There is a need to establish new management options as current treatment is frequently suboptimal. Clinical approaches based on autologous stem cell transplant is potentially a good alternative. The heart was long considered an organ unable to regenerate and renew. However, several reports imply that it may possess modest intrinsic regenerative potential. To allow for detailed characterization of cell cultures, whole transcriptome profiling was performed after 0, 7, 15, and 30 days of in vitro cell cultures (IVC) from the right atrial appendage and right atrial wall utilizing microarray technology. In total, 4239 differentially expressed genes (DEGs) with ratio > abs |2| and adjusted p-value ≤ 0.05 for the right atrial wall and 4662 DEGs for the right atrial appendage were identified. It was shown that a subset of DEGs, which have demonstrated some regulation of expression levels with the duration of the cell culture, were enriched in the following GO BP (Gene Ontology Biological Process) terms: "stem cell population maintenance" and "stem cell proliferation". The results were validated by RT-qPCR. The establishment and detailed characterization of in vitro culture of myocardial cells may be important for future applications of these cells in heart regeneration processes.
Asunto(s)
Regulación de la Expresión Génica , Miocitos Cardíacos , Transcriptoma , Animales , Porcinos , Miocitos Cardíacos/metabolismo , Técnicas de Cultivo de Célula , Perfilación de la Expresión GénicaRESUMEN
Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers-CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton's jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.
Asunto(s)
Células Madre Mesenquimatosas , Gelatina de Wharton , Humanos , Transcriptoma , Condrocitos , Diferenciación Celular/genética , Adipocitos , Apoptosis/genética , Osteoblastos , Células Cultivadas , Proteínas del Tejido NerviosoRESUMEN
OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder described by the dynamic decline of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Stem cell transplantation is a new therapeutic strategy in the treatment of PD. The objective of the study was to assess the impact of intravenous infusion of adipose-derived mesenchymal stem cells (AD-MSCs) on memory disorder in Parkinsonian rats. MATERIALS AND METHODS: In this experimental study, male Wistar rats were randomly divided to four groups containing sham, cell treatment, control, and lesion. The cell treatment group received intravenous injection of AD-MSCs 12 days after PD induction by bilateral injection of 6-hydroxydopamine. Four weeks after lesion formation, spatial memory was examined using the Morris water maze (MWM) assessment. The rats' brains were removed and assessed by bromodeoxyuridine (BrdU), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (Gfap) immunostaining. RESULTS: Statistical analyses revealed a significant addition and reduction in time spent and escape latency in the target quadrant, respectively, in the cell group as compared to the lesion group. Also, BrdU-labeled cells were present in the substantia nigra (SN). The density of TH-positive cells was significantly increased in the AD-MSCs transplantation group as compared to the lesion group, and the density of astrocytes significantly diminished in the AD-MSCs transplantation group as compared to the lesion group. CONCLUSION: It appears that AD-MSCs treatment for Parkinson's could decrease the density of astrocytes and promote the density of TH-positive neurons. It appears that AD-MSCs could improve spatial memory impairment in PD.
RESUMEN
Primordial germ cells (PGCs), are the source of gametes in vertebrates. There are similarities in the development of PGCs of reptiles with avian and mammalian species PGCs development. PGCs culture has been performed for avian and mammalian species but there is no report for reptilian PGCs culture. In vitro culture of PGCs is needed to produce transgenic animals, preservation of endangered animals and for studies on cell behaviour and research on fertility. Reptiles are traded as exotic pets and a source of food and they are valuable for their skin and they are useful as model for medical research. Transgenic reptile has been suggested to be useful for pet industry and medical research. In this research different aspects of PGCs development was compared in three main classes of vertebrates including mammalian, avian and reptilian species. It is proposed that a discussion on similarities between reptilian PGCs development with avian and mammalian species helps to find clues for studies of reptilian PGCs development details and finding an efficient protocol for in vitro culture of reptilian PG.