Current Stem Cell Research & Therapy - Online First

Idiopathic Nephrotic Syndrome (INS) is a common kidney disease in children, and the main clinical manifestations are hypoproteinaemia, proteinuria, hyperlipidaemia, and oedema. Mesenchymal Stem Cells (MSCs) are involved in tissue repair, protection against fibrosis, and immune modulation but have rarely been studied in INS.

This study aimed to explore the therapeutic potential of stem cells derived from human exfoliated deciduous teeth (SHEDs) in INS using an adriamycin-induced nephropathy (AN) rat model.

AN was induced in Sprague‒Dawley rats, and SHEDs were transplanted via the tail vein in single (SHED-s) and multidose (SHED-m) regimens. Cell migration assays were used to track the SHED distribution. Weight, urine protein, and serum biochemical assays were also performed. HE and Masson staining were used to observe glomerular and tubular damage, as well as the degree of fibrosis. Immunohistochemistry was used to label T lymphocytes and podocytes, and structural changes in podocytes were observed by electron microscopy. ELISA was used to measure the levels of inflammatory factors. Flow cytometry was used to analyse the balance of Th17 cells and Tregs. The mRNA expression of Th17- and Treg-associated cytokines and specific transcription factors was examined by RT‒PCR.

SHEDs directly migrated to damaged tissues, suggesting a targeted therapeutic effect. SHED transplantation significantly reduced proteinuria and reversed biochemical abnormalities in rats with AN. Both single and multidose SHED treatments could inhibit glomerular and tubular damage and delay the progression of fibrosis caused by adriamycin. SHEDs exerted a protective effect on podocytes. Additionally, this treatment inhibited inflammatory responses and corrected immune imbalances, as evidenced by decreased T lymphocyte infiltration, reduced serum levels of IL-6, TNF-a, and IL-1β, and modulation of the Th17/Treg balance.

In the AN rat model, SHED partly suppressed the development of inflammation and alleviated kidney injury, and immune regulation may be the underlying mechanism.

Human adipose-derived stem cells (hADSCs) are considered a promising source for cell replacement therapy in degenerative and traumatic conditions. This study explores the effects of phenylacetate and calcium on the neural differentiation of hADSCs for regenerative medicine. We assessed cell viability and cytotoxicity using the MTT assay, revealing that treatment with 1μM phenylacetate significantly enhanced cell viability compared to control groups over five days, while higher concentrations resulted in cytotoxic effects.

Additionally, qualitative analysis through Acridine orange/ethidium bromide (AO/EB) staining indicated normal cellular characteristics at lower phenylacetate concentrations, whereas higher doses led to observable cell death. A subsequent evaluation of intracellular calcium levels demonstrated a significant increase when hADSCs were treated with both phenylacetate and calcium.

The neural differentiation potential was further assessed through the relative quantification of neuronal-specific genes, showing marked upregulation of NSE, Oligo-2, β-tubulin III, and MAP-2 in all treatment groups compared to controls. Immunohistochemistry confirmed elevated protein expression of neural markers in cultures supplemented with phenylacetate and calcium.

These findings suggest that phenylacetate, particularly in conjunction with calcium, enhances the neural differentiation of hADSCs, highlighting its potential utility in regenerative medicine strategies targeting neurodegenerative conditions.

Trigeminal Neuralgia (TN) is an extremely painful condition without an established treatment other than symptom-suppressive medications or temporary relief from corticosteroid injections. Mesenchymal Stem Cells (MSCs) have demonstrated the ability to enhance healing and reduce inflammation and pain without side effects. Our objective was to evaluate the safety and efficacy of CT-guided foramen ovale MSC injection in the treatment of TN.

A 48-year-old woman presented with a 22-year history of severe TN. Previous treatments, including microvascular decompression, acupuncture, chiropractic adjustment, and hypnotism had failed. Medications decreased pain, but produced severe bothersome mental clouding. After proper informed consent, the patient elected trigeminal nerve injection in the foramen ovale with AlloRx (vitrobiopharma.com Golden Colorado) umbilical cord-derived Mesenchymal Stem Cells (MSCs). An experienced pain specialist with previous experience using CT guidance with sedation to inject the trigeminal nerve in the foramen ovale with corticosteroids performed the injection using 20 million MSCs. The patient reported no adverse events or complications related to the treatment.

At 1 month post-treatment, the patient reported dramatically reduced pain/tingling, and no longer needed medication, which resulted in the resolution of her mental clouding. At 12 months post-treatment, some symptoms recurred, but the patient maintained substantial cognitive improvements and required a reduced dose of medication.

We have demonstrated, for the first time, CT-guided MSC injection into the foramen ovale to result in significant improvement in trigeminal neuralgia without side effects.

With the passage of time, the incidence rate of diabetes continues to rise. As a common and serious complication of diabetes, the economic burden of diabetes ulcers is also increasing. However, there is currently no unified clinical treatment strategy for its repair and research, and the treatment effect is not satisfactory. Exosomes derived from MSCs play a crucial role in improving diseases.

This study used the explant culture method to isolate human umbilical cord mesenchymal stem cells (hucMSCs) from Wharton’s jelly, which were identified by flow cytometry and differentiation potential and evaluated tumorigenic potential. The supernatant of P3-P5 cell culture medium was collected and high-concentration human umbilical cord mesenchymal stem cell exosomes (hucMSCs-Exos) were isolated through ultracentrifugation. Qualitatively identified were finished by transmission electron microscopy (TEM), nanosight tracking analysis (NTA) and Western blot (WB). CCK-8 assay and cell scratch experiment were used to evaluate the effects of hucMSCs-Exos on proliferation and migration ability of cells; chicken embryo chorioallantoic membrane experiment (CAM) was used to evaluate the angiogenic effect of hucMSCs-Exos. In order to study the effect of hucMSCs-Exos on diabetes wound healing, the diabetes mouse model was constructed by a high-fat feeding and a low-dose STZ injection. Fasting blood glucose and blood lipids were measured and oral glucose tolerance test (OGTT) was conducted; HucMSCs-Exos were subcutaneously injected into the T2DM wound model mice which were established by a high-fat diet and by a low-dose streptozotocin (STZ), and the wound healing was evaluations.

Cells were isolated by explant culture method, and flow cytometry analyses showed that these isolated cells were positive for cells markers CD29, CD90, and CD105, while negative for CD34 and CD45; moreover, these cells could be induced to osteoblasts, adipocytes, and islet-like cells. The tumorigenic experiments showed that these cells have no tumorigenicity. HucMSCs-Exos, separated by ultracentrifugation, displayed spherical or ellipsoidal vesicles with a diameter of around 120nm, positive for CD9, CD63, and CD81. And they could promote cell proliferation and migration, as well as promote vascular growth (p < 0.01). In vivo experiments showed that hucMSCs-Exos had a promoting effect on wound repair in diabetes mellitus type 2 (T2DM) mice (p < 0.01).

This study provides a new scheme for the treatment of T2DM ulcer.