Jentashapir Journal of Cellular and Molecular Biology
Volume:16 Issue: 1, Mar 2025

Context: 

Recent advances in induced pluripotent stem cells (iPSCs), CRISPR-Cas9 gene editing, nanotechnologies, and artificial intelligence have revolutionized regenerative medicine (RM) as a transformative field for tackling difficult medical problems. These breakthroughs promise specific treatments, proper restoration of tissue function, and substantial improvements in the quality of life for patients whose ailments cannot yet be cured.This review explores cutting-edge advancements in RM platforms such as stem cell therapy, gene editing, 3D bioprinting, and nanotechnology. The study also aims to shed light on the challenges of clinical translation and policy implications, which are crucial for fostering sustainable and progressive advances in the discipline. 

Evidence Acquisition: 

This manuscript draws on cutting-edge research on the development and application of RM technologies. It synthesizes data on stem cells, gene therapy, tissue engineering, the in vitro organoid industry, artificial intelligence (AI), and nanotechnology that illustrate therapeutic potential. It also aims to identify ethical, regulatory, and practical hurdles for translating RM from research to clinical practice.

Breakthroughs such as those in iPSC-derived organoids, CRISPR-Cas9 gene editing, 3D bioprinting, and nanostructured materials exhibit significant promise in preclinical and clinical settings. Platforms such as organ-on-chip and AI tools further enhance drug discovery and treatment monitoring, while biomaterials and scaffold-based approaches enhance tissue repair and regeneration. Nevertheless, despite these advances, challenges persist regarding scale-up, safety, and ethical considerations.

Innovations in RM represent a paradigm shift from purely symptomatic treatments to restorative therapies. Successful integration of RM into clinical practice will require multidisciplinary collaborative work, imposition of rigorous safety protocols, and enabling regulatory frameworks. Addressing these challenges would enable RM to realize its true potential as a foundation for 21st-century healthcare.

The global surge in diabetes presents a significant healthcare challenge. Viral infections complicate diabetes by influencing systemic metabolism and disrupting glycemic control in type 2 diabetes (T2D). High glucose levels impair macrophage activity, raising the risk of chronic infections. Viral-induced type-I immune responses initiate insulin resistance, which affects muscle, liver, and pancreatic functions. Diabetogenic viruses impair pancreatic cells or affect gut microbiota. Viral survival tactics disrupt antigen presentation and use viral miRNAs to target diabetes-related gene expression. The hidden association between latent viruses, particularly herpesviruses like Human Cytomegalovirus (HCMV), and diabetes is explored, emphasizing CMV's role in type 1 diabetes (T1D) pathogenesis. Inflammatory pathways triggered by viral infections play a critical role in islet-specific autoimmunity and the development of T1D. The HCMV’s pervasive reach, from local areas to the entire body, involves infected monocytes infiltrating organs, persisting in the bone marrow, and enabling virus spread during reactivation events. When a viral infection occurs, the immune system mounts a type 1 response characterized by the activation of CD4+ T-cells and the production of pro-inflammatory cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). These cytokines can lead to the recruitment of immune cells to pancreatic islets, resulting in inflammation and damage to insulin-producing beta cells. Furthermore, the chronic inflammation caused by sustained cytokine release can impair insulin signaling pathways. Specifically, pro-inflammatory cytokines interfere with insulin receptor substrate (IRS) proteins, leading to decreased insulin sensitivity in peripheral tissues such as muscle and adipose tissue. This cascade of events ultimately contributes to the development of insulin resistance, setting the stage for T2D. This investigation highlights the complex relationship between viral infections and diabetes. Research indicates that viral infections can increase the risk of developing T2D.

In recent years, scientists have focused on the use of natural ingredients, including herbal extracts, in the treatment of breast cancer.

This study aimed to evaluate the cytotoxic effects of the aqueous extract of sweet pomegranate seed (AESPS) and vitamin D on MCF-7 breast cancer cells and human fibroblast cells for the first time.

MCF-7 and fibroblast cells were cultured in 96-well plates at a density of 10 4 cells/well and treated with different concentrations of AESPS and vitamin D (25, 50, 100, and 200 mg/mL). Cell viability was assessed using methylthiazol tetrazolium (MTT) assays at 24, 48, and 72 hours. The data were analyzed using statistical tests with a significance level of 0.05.

The results showed that AESPS inhibited the viability of MCF-7 cells, especially at a concentration of 200 mg/mL for 24 hours. In contrast, 200 mg/mL of vitamin D resulted in an increase in cell death of MCF-7 cells after 48 hours. Additionally, AESPS did not cause any significant toxicity to fibroblast cells, while vitamin D caused approximately 30% toxicity to fibroblast cells after 48 hours.

Therefore, this herbal extract has a significant cytotoxic effect on MCF-7 cancer cells, even more so than vitamin D, and a non-cytotoxic effect on human fibroblast cells, significantly less than vitamin D. Aqueous extract of sweet pomegranate seed could be utilized in the treatment of breast cancer with further research in animal models and, eventually, clinical trials.

The peptide HL-10, derived from the venom of Hemiscorpius lepturus , has several biological functions, notably its ability to inhibit cancer growth.

This research aimed to evaluate the tumor-suppressing properties of the HL-10 peptide in SiHa cancer cells, investigating its effects in both in vitro and in vivo models.

The study assessed cytotoxicity using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, analyzed gene expression through real-time PCR, and measured caspase activity via ELISA to gain insights into the peptide's mechanisms of action. For in vivo experiments, BALB/c mice bearing SiHa cervical cancer were used. The ELISA technique was employed to evaluate the activity levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes in serum, as well as the concentrations of intra-tumoral cytokines, including TNF-α, IFN-γ, IL-1β, IL-4, and IL-10.

Our results demonstrated a significant (P < 0.05) dose- and time-dependent decrease in the viability percentage of SiHa cancer cells. The analysis revealed a marked upregulation in the expression of p53, cyt c, bax, caspase-3, and caspase-9 genes as the peptide concentration was elevated from 5 to 10 μM. In contrast, there was a significant decrease (P < 0.05) in bcl-2 gene expression, while caspase-8 gene expression showed no significant change (P > 0.05). The analysis of caspase activity indicated a significant rise (P < 0.05) in the activities of caspase-9 and caspase-3 in cancer cells exposed to the HL-10 peptide, while the activity of caspase-8 remained unchanged. The findings from in vivo experiments conducted on cancer mice demonstrated a substantial reduction in tumor volume over time in cancer mice treated with HL-10 peptide plus carboplatin (5 mg/kg) compared to cancer mice that were not treated (P < 0.05). In comparison to untreated cancer mice, the tumor microenvironment of cancer mice treated with HL-10 peptide and carboplatin exhibited a substantial increase in IL-1β, IFN-γ, and TNF-α levels. The levels of IL-4 and IL-10 in the tumor were significantly reduced (P < 0.05), indicating a substantial decrease in these cytokines. This reduction suggests potential modulation of the tumor microenvironment in response to the treatment.

In conclusion, this research showed that the HL-10 peptide effectively initiates apoptosis and inhibits the proliferation of SiHa cervical cancer cells through the activation of the mitochondrial signaling cascade. Additionally, the HL-10 peptide is believed to contribute to cancer immunotherapy by modulating the immune system.

Breast carcinoma (BC) is the most prevalent form of cancer in women and is classified into various subtypes based on the expression of ER, PR, and human epidermal growth factor 2 (HER2) receptors. Human epidermal growth factor 2-positive BC, in particular, presents significant challenges due to its aggressiveness and limited treatment options. Modulating apoptotic pathways is crucial for reducing tumor burden and enhancing treatment efficacy.

This study aimed to evaluate the inhibitory effects of secretomes derived from Wharton's jelly mesenchymal stem cells (WJ-MSC secretomes) on the proliferation of the SKBR3 cell line, as well as the subsequent changes in apoptosis-related gene expression after treatment. The research provides new insights into the therapeutic potential of WJ-MSC secretomes for HER2-positive BC.

SKBR3 cells were exposed to WJ-MSC secretomes at doses of 10, 25, and 50 μg/mL for 24 and 48 hours. MTT assays and colony formation assays were used to evaluate cell viability, while annexin V/PI staining and mRNA expression analyses were conducted to assess apoptosis.

Treatment with WJ-MSC secretomes led to a significant, concentration- and time-dependent reduction in colony numbers and cell viability in the 25 and 50 μg/mL groups. Early and late apoptotic indices increased significantly in the 25 μg/mL group, with P-values of < 0.01 and < 0.05, respectively. The mRNA expression levels of Caspase-9 (P < 0.001), Caspase-3 (P < 0.05), and the Bax/Bcl-2 ratio (P < 0.01) significantly increased in the 25 μg/mL treatment group. Caspase-8 activity was unaffected by WJ-MSC secretomes.

Wharton's jelly mesenchymal stem cells secretomes demonstrate potential as an anticancer agent for HER2-positive BC, acting through the intrinsic apoptotic pathway in a concentration- and time-dependent manner. This study is the first to detail the specific effects of WJ-MSC secretomes on HER2-positive SKBR3 cells, suggesting their novel application in targeted breast cancer therapy.

Extensive evidence demonstrates that neuronal autophagic and cytoskeletal elements play critical roles in neuroplasticity. Dysregulation of neuroplasticity has been implicated in the pathology of depression and post-traumatic stress disorder (PTSD). Transcription factor EB (TFEB) and stathmin are key regulators of autophagy and microtubule formation, respectively.

The current study aimed to compare the levels of hippocampal TFEB and stathmin proteins in PTSD and depressed animal models of rats.

Three groups of male rat pups (n = 8) were used. The first group, designated as the depressed group, was exposed to maternal separation stress and related stressors. The second group, representing the PTSD model, was exposed to single-prolonged stress. The third group served as the control. Anxiety-like and depressive-like behaviors were evaluated using the elevated plus maze (EPM) and forced swimming test (FST). Hippocampal TFEB and stathmin protein levels were measured using western blotting. Data were analyzed using Prism software. One-way ANOVA and post hoc Tukey tests were performed to evaluate statistical differences between groups in behavioral tasks. Independent t -tests were used to assess differences in protein levels between groups.

The TFEB protein levels were increased in both PTSD and depressed rats, while stathmin levels were decreased. The effect of depression on TFEB expression was significantly higher than in PTSD. Conversely, stathmin reduction was more pronounced in PTSD compared to depressed rats.

These results suggest that changes in stathmin and TFEB protein levels may be associated with anxiety- and depression-like behaviors.