- Volume 20, Issue 9, 2025

Premature Ovarian Failure (POI), a prevalent gynecological, endocrine disease, significantly impairs the reproductive health of women of childbearing age and presents a formidable challenge to clinicians. Until now, there has been a lack of effective treatments to fundamentally improve ovarian function in patients with POI. Stem cell therapy has emerged as a promising treatment in the field of POI, with notable research progress achieved to date.

This review sought to analyze the current status and hotspots of research on stem cell therapy for POI, forecasting future directions through bibliometrics.

Research related to stem cell therapy for POI from 2000 to 2023 was searched in the Web of Science Core Collection (WOSCC) database by setting subject-term, and the literature was analyzed econometrically using VOSviewer, CiteSpace, and the R package “bibliometrix.”

According to our search and screening strategy, 203 pieces of literature related to stem cell therapy for POI were obtained and analyzed. There is a marked annual increase in publications, with a particularly rapid ascent in recent years. China has become the most prolific country in this field, with 136 publications. Shanghai Jiao Tong University ranked first among many universities and institutions in terms of the number of publications and citations. Stem Cell Research & Therapy was the most popular and influential journal in the field of stem cell therapy for POI. Lai Dongmei has published the most papers, while Liu Te boasts the highest frequency of co-citations. Investigation into the mechanisms of exosomes derived from stem cells and their associated signaling pathways is anticipated to be a crucial research topic in stem cell therapy for POI.

This review offers the first comprehensive and systematic analysis of the field of stem cell therapy for POI, with a visual representation of the findings. By summarizing the current status and projecting forthcoming trends, this study aims to offer guidance and a reference for scholars in the field.

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.

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.

The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection. This study aimed to investigate the protective effect of Sema3A on the osteogenic differentiation of PDLSCs under OS conditions induced by hydrogen peroxide (H2O2).

PDLSCs were subjected to H2O2 treatment to induce OS. The OS indices in PDLSCs were evaluated by analyzing levels of reactive oxygen species (ROS), cell viability, and expression of antioxidant factors using relevant assay kits. A small molecule inhibitor, XAV-939, was employed to block the Wnt/β-catenin pathway. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining for mineralized nodules. Expression levels of osteogenic gene markers and β-catenin were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis.

The stimulation of H2O2 induced OS in PDLSCs, resulting in a downregulation of Sema3A expression and a decrease in osteogenic markers, including ALP activity, mineralized nodule formation, and the expression of osteogenic genes (RUNX2 and ALP). However, the application of recombinant human Sema3A (rhSema3A) counteracted H2O2-induced OS and restored these osteogenic markers in PDLSCs under OS induced by H2O2. Mechanistic studies revealed that these effects were associated with an upregulation of β-catenin levels. Moreover, inhibiting β- catenin expression compromised the protective effect of Sema3A on osteogenesis in PDLSCs under OS.

Sema3A exerts a protective effect against H2O2-induced OS and activates the Wnt/β- catenin pathway to restore osteogenic differentiation impaired by OS in PDLSCs.

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 had 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 resulting in 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 that CT guided MSC injection into the foramen ovale results in significant improvement in trigeminal neuralgia without side effects.