Current Stem Cell Research & Therapy - Online First

Osteoarthritis (OA) is a degenerative joint disease that can affect the many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical use at this time probably due to a lack of complete comprehension of the pathogenesis of the disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated and differentiated cells have gained much attention as they can efficiently promote tissue repair and regeneration.

To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x10⁶ cells/rat/dose for three weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric, ELISA, and Western blot analyses were applied to detect various immunological and molecular parameters in serum and ankle.

The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor (RF), prostaglandin E2 (PGE2) and interleukin (IL-) 1β levels, while they elevated serum IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities. The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid 2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.

According to these findings, it can be inferred that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results, BM-MSCs and CD-MSCs therapies are promising new options that can be associated with other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical and clinical research is required to assess the benefits and safety of treating osteoarthritic patients with BM-MSCs and CD-MSCs.

This study aims to explore the therapeutic potential of mesenchymal stem cells (MSC) in treating diabetic nephropathy (DN) by investigating their effect on IL-11 modulation in a mouse model.

The effects of MSC therapy on DN were examined both in vivo and in vitro. Sixty adult male C57BL/6 mice were divided into the streptozotocin (STZ) diabetes (T1D) and the high-fat diet diabetes (T2D) models, with both groups receiving MSC treatment or saline for 4 or 8 weeks. Blood glucose, serum urea, interleukin-11 (IL-11), and kidney fibrosis markers were measured. Additionally, western blotting was used to assess levels of Type I and III collagen, E-Cadherin, α-smooth muscle actin (α-SMA), Vimentin, and ferroptosis suppressor protein 1 (FSP-1).

MSC-treated T1D and T2D mice showed reduced blood glucose, serum urea, IL-11, TGF-β, and fibrosis markers (type I and III collagen, α-SMA, Vimentin, FSP-1), alongside increased E-Cadherin expression. Similar effects were observed in vitro using mouse glomerular epithelial cells, confirming MSC-mediated suppression of fibrosis pathways.

MSC therapy improves nephropathy, likely by inhibiting IL-11 and reducing fibrosis-related markers, making it a promising treatment for DN.

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.