Current Stem Cell Research & Therapy - Current Issue

Organoids are three-dimensional structures that faithfully mimic the intricate internal environment of the human body. Compared to conventional models, they demonstrated superior performance. Recently, they have emerged as valuable platforms for modeling obesity-related diseases and advancing therapeutic strategies.

This review not only aimed to simply discuss the limitations of 2D cellular and animal models for obesity-related diseases but also highlighted the importance of developing organoids to better understand the relationship between obesity, lipid metabolism, glucose homeostasis, and chronic inflammation. It also identifies the challenges and potential directions for organoid applications in these diseases.

We searched for keywords related to organoids, obesity, lipid metabolism, glucose homeostasis, chronic inflammation, disease models, and drug screening in scientific research databases.

Organoids have emerged as promising tools for investigating the pathophysiology of diseases and developing therapeutic interventions. They have effectively bridged the gap in research on obesity-related diseases between conventional experimental models and the human body. They could offer more efficient and physiologically relevant experimental models while also improving the treatment efficacy for individuals with obesity-related conditions.

Organoids are beneficial for investigating obesity-related diseases. However, it is imperative to implement standardised culture procedures to improve reproducibility and broaden their application. Combining medicine and science to create these processes and minimise variation can increase the reliability and consistency of organoid cultures and provide new opportunities for addressing obesity-related diseases.

Pulmonary fibrosis, a condition characterized by excessive lung tissue scarring, remains a significant therapeutic challenge. Given the potential of human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) and their small extracellular vesicles (hWJ-MSC-EVs) as minimally invasive and scalable therapeutic options for pulmonary fibrosis in clinical settings, this study investigates the potential of hWJ-MSCs and hWJ-MSC-EVs in mitigating bleomycin-induced lung injury in C57BL/6J mice.

hWJ-MSCs were cultured and characterized for their ability to differentiate into osteogenic, adipogenic, and chondrogenic lineages. EVs were successfully induced via serum starvation, purified using ultracentrifugation, and characterized for their protein and nucleic acid content, size distribution, and EV markers. A bleomycin-induced pulmonary fibrosis model was established in C57BL/6J mice. Mice were monitored for weight loss, mortality, and lung fibrosis severity following treatment with hWJ-MSCs and hWJ-MSC-EVs. Histological analysis and Ashcroft scoring were used to assess lung fibrosis.

Bleomycin administration in mice resulted in significant weight loss, increased mortality, and severe lung fibrosis, as demonstrated by histological analysis and Ashcroft scoring. Treatment with hWJ-MSCs and hWJ-MSC-EVs significantly alleviated these symptoms. Mice receiving these treatments exhibited improved body weight, enhanced survival rates, and reduced lung fibrosis, with notable improvements in alveolar structure and decreased fibrotic tissue deposition.

These findings highlight the potential of hWJ-MSCs and hWJ-MSC-EVs as therapeutic agents in treating pulmonary fibrosis by reducing inflammation and promoting lung tissue repair, offering a potential new avenue for regenerative therapy in severe lung diseases. Future research directions involve elucidating the molecular pathways involved in tissue repair, optimizing therapeutic delivery, and conducting comprehensive clinical evaluations.

Mesenchymal stem cells (MSCs) were able to restore ovarian function in premature ovarian insufficiency (POI), which can be largely attributed to the paracrine effects of MSCs therapy. However, the function and mechanism of MSC-derived exosomes transplantation for POI are not fully understood.

To investigate the efficacy and underlying mechanisms of human placental derived MSCs derived exosomes (hpMSC-Exos) xenotransplantation in incremental load training-induced POI.

The incremental exercise treadmill training was employed for constructing the POI rat model. hpMSC-Exos were administered to POI rats by tail vein injection. The ovarian function was assessed based on histological analysis and hormone levels. Ovarian function parameters, follicle counts, oocyte aging, granulosa cell apoptosis, and follicular microenvironment were evaluated.

The tracking of hpMSC-Exos indicated that they generally colonized the ovarian tissues. hpMSC-Exos transplantation increased telomere length and telomerase activity, reduced oxidative stress, downregulated the Bax and caspase-3 gene expression, upregulated the Bcl-2 gene expression, and increased the insulin-like growth factor 1 (Igf-1) and vascular endothelial growth factor (VEGF) expression level. Furthermore, the findings showed that the follicle-stimulating hormone (FSH) level and FSH to luteinizing hormone (LH) ratio were decreased, whereas the population of follicles significantly increased after transplantation.

hpMSC-Exos transplantation was observed to improve the function of the injured ovarian tissues in the incremental load training-induced POI rats. Furthermore, the mechanisms of hpMSC-Exos are related to delaying aging in the oocyte, reducing apoptosis of granulosa cells, and regulating the follicular microenvironment.

Burn injuries pose a significant health challenge, leading to intense physiological stress compared to other types of trauma. Myrtle has been traditionally used for treating various skin ailments, while mesenchymal stem cells (MSCs) have introduced innovative approaches for burn treatment. This study aimed to evaluate the impact of myrtle compared to MSCs on the healing of deep second-degree burns.

Fifty adult male albino rats were randomly divided into five groups: Group A served as the control, Group B received an excision burn without treatment, Group C was treated with topical myrtle paste, Group D received an intradermal injection of mesenchymal stem cells (MSCs), and Group E received both topical myrtle paste and intradermal MSC injection. Burn healing was assessed based on visible characteristics over 21 days. At the end of the treatment, skin samples were collected for biochemical analysis, histological examination using hematoxylin and eosin (H&E) staining, and VEGF concentration measurement via ELISA. Additionally, PCR analysis was conducted to assess the expression levels of COL1a1, COL3a1, TNF-α, and IL-6, providing insights into collagen production and inflammatory response.

Gross evaluation and histopathological analysis indicated that Groups D and E exhibited complete skin regeneration compared to the burn group. VEGF analysis demonstrated enhanced angiogenesis in the treated groups. PCR analysis revealed upregulation of COL1a1 and COL3a1, along with downregulation of TNF-α and IL-6, suggesting reduced inflammation and improved skin healing.

The study demonstrated that both MSCs and myrtle contributed to significant burn healing. The combination of myrtle and MSCs (Group E) exhibited the most effective skin regeneration, likely due to enhanced collagen production, reduced inflammation, and improved angiogenesis. These findings suggest that combining traditional herbal treatments with stem cell therapy may offer a promising strategy for burn management.