Therapeutic and diagnostic applications of exosomes in colorectal cancer.

Exosomes play a key role in colorectal cancer (CRC) related processes. This review explores the various functions of exosomes in CRC and their potential as diagnostic markers, therapeutic targets, and drug delivery vehicles. Exosomal long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) significantly influence CRC progression. Specific exosomal lncRNAs are linked to drug resistance and tumor growth, respectively, highlighting their therapeutic potential. Similarly, miRNAs like miR-21, miR-10b, and miR-92a-3p, carried by exosomes, contribute to chemotherapy resistance by altering signaling pathways and gene expression in CRC cells. The review also discusses exosomes' utility in CRC diagnosis. Exosomes from cancer cells have distinct molecular signatures compared to healthy cells, making them reliable biomarkers. Specific exosomal lncRNAs (e.g., CRNDE-h) and miRNAs (e.g., miR-17-92a) have shown effectiveness in early CRC detection and monitoring of treatment responses. Furthermore, exosomes show promise as vehicles for targeted drug delivery. The potential of mesenchymal stem cell (MSC)-derived exosomes in CRC treatment is also noted, with their role varying from promoting to inhibiting tumor progression. The application of multi-omics approaches to exosome research is highlighted, emphasizing the potential for discovering novel CRC biomarkers through comprehensive genomic, transcriptomic, proteomic, and metabolomic analyses. The review also explores the emerging field of exosome-based vaccines, which utilize exosomes' natural properties to elicit strong immune responses. In conclusion, exosomes represent a promising frontier in CRC research, offering new avenues for diagnosis, treatment, and prevention. Their unique properties and versatile functions underscore the need for continued investigation into their clinical applications and underlying mechanisms.

Development and validation of Alzheimer's Disease Animal Model for the Purpose of Regenerative Medicine.

One of the most common age-related neurodegenerative disorders is Alzheimer's disease which globally threatening the health of elderly people. Although there are several pharmacological and non- pharmacological treatments for Alzheimer's disease, they can just decrease the symptoms in these diseases. In this context, cell therapy and regenerative medicine approach as the novel therapeutic strategies for neurodegenerative diseases would be important. Based on scientific research principles, using any novel therapeutic approaches before the run in clinical trials need to take preclinical (animal study) stapes. Accordingly, an animal study can improve our understanding of biological mechanisms of diseases and as an important step should adhering to ethical guidelines and standards. On the other hand, to gain suitable outcomes, it is important to check the appropriate validation of animal models. In this regard, the present review would discuss about the development and validation of appropriate AD animal models in the field of regenerative medicine.

Metabolomics Analysis of Mesenchymal Stem Cells.

Various mesenchymal stem cells as easily accessible and multipotent cells can share different essential signaling pathways related to their stemness ability. Understanding the mechanism of stemness ability can be useful for controlling the stem cells for regenerative medicine targets. In this context, OMICs studies can analyze the mechanism of different stem cell properties or stemness ability via a broad range of current high-throughput techniques. This field is fundamentally directed toward the analysis of whole genome (genomics), mRNAs (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in biological samples. According to several studies, metabolomics is more effective than other OMICs ّfor various system biology concerns. Metabolomics can elucidate the biological mechanisms of various mesenchymal stem cell function by measuring their metabolites such as their secretome components. Analyzing the metabolic alteration of mesenchymal stem cells can be useful to promote their regenerative medicine application.

Metabolomics and Cell Therapy in Diabetes Mellitus.

Diabetes with a broad spectrum of complications has become a global epidemic metabolic disorder. Till now, several pharmaceutical and non-pharmaceutical therapeutic approaches were applied for its treatment. Cell-based therapies have become promising methods for diabetes treatment. Better understanding of diabetes pathogenesis and identification of its specific biomarkers along with evaluation of different treatments efficacy, can be possible by clarification of specific metabolic modifications during the diabetes progression. Subsequently, metabolomics technology can support this goal as an effective tool. The present review tried to show how metabolomics quantifications can be useful for diabetic monitoring before and after cell therapy. Cell therapy is an alternative approach to achieve diabetes treatments goals including insulin resistance amelioration, insulin independence reparation, and control of glycemia. OMICs approaches provide a comprehensive insight into the molecular mechanisms of cells features and functional mechanism of their genomics, transcriptomics, proteomics, and metabolomics profile which can be useful for their therapeutic application. As a modern technology for the detection and analysis of metabolites in biological samples, metabolomica can identify many of the metabolic and molecular pathways associated with diabetes and its following complications.

Differentiation potential of human CD133 positive hematopoietic stem cells into motor neuron- like cells, in vitro.

Spinal cord injuries and motor neuron-related disorders impact on life of many patients around the world. Since pharmacotherapy and surgical approaches were not efficient to regenerate these types of defects; stem cell therapy as a good strategy to restore the lost cells has become the focus of interest among the scientists. Umbilical cord blood CD133+ hematopoietic stem cells (UCB- CD133+ HSCs) with self- renewal property and neural lineage differentiation capacity are ethically approved cell candidate for use in regenerative medicine. In this regard the aim of this study was to quantitatively evaluate the capability of these cells to differentiate into motor neuron-like cells (MNL), in vitro. CD133+ HSCs were isolated from human UCB using MACS system. After cell characterization using flow cytometry, the cells were treated with a combination of Retinoic acid, Sonic hedgehog, Brain derived neurotrophic factor, and B27 through a 2- step procedure for two weeks. The expression of MN-specific markers was examined using qRT- PCR, flow cytometry and immunocytochemistry. By the end of the two-week differentiation protocol, CD133+ cells acquired unipolar MNL morphology with thin and long neurites. The expression of Isl-1(62.15%), AChE (41.83%), SMI-32 (21.55%) and Nestin (17.46%) was detected using flow cytometry and immunocytochemistry. The analysis of the expression of PAX6, ISL-1, ACHE, CHAT and SMI-32 revealed that MNLs present these neural markers at levels comparable with undifferentiated cells. In Conclusion Human UCB- CD133+ HSCs are remarkably potent cell candidates to transdifferentiate into motor neuron-like cells, in vitro.

A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells.

OBJECTIVE: Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine. MATERIALS & METHODS: To do that, neonate placenta Umbilical Cord Blood were transferred to the lab. After characterization of the isolated cells using flowcytometry and multilineage differentiation capacity, the obtained Mesenchymal Stem Cells were cultured in DMEM/F12 supplemented with 2% FBS and 10µM of 5-azacytidine to induce myogenic differentiation. Real-time PCR and immunocytochemistry were used to assess the myogenic properties of the cells. RESULTS: Our data showed that C-MSCs and UCB-MSCs were spindle shape in morphology. They were positive for CD90, CD73 and CD44 antigens, and negative for hematopoietic markers. They also differentiated into osteoblast and adipoblast lineages. Real-time PCR results showed that the cells could express MyoD, desmin and α-MHC at the end of the first week (P<0.05). No significant upregulation was detected in the expression of GATA-4 in both groups. Immunocytochemical staining revealed the expression of Desmin, cTnT and α-MHC. CONCLUSIONS: Results showed that these cells are potent to differentiate into myoblast- like cells. An upregulation in the expression of some myogenic markers (desmin, α- MHC) was observed in C-MSCs in comparison with UCB-MSCs.