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Placenta-derived mesenchymal stem cells (PD-MSCs) have numerous advantages over other adult MSCs that make them an attractive cell source for regenerative medicine. Here, we demonstrate the therapeutic effect of PD-MSCs in ovariectomized (Ovx) rats and compare their efficacy when generated via a conventional monolayer culture system (2D, naïve) and a spheroid culture system (3D, spheroid). PD-MSC transplantation significantly increased the estradiol level in Ovx rats compared with the non-transplantation (NTx) group. In particular, the estradiol level in the Spheroid group was significantly higher than that in the Naïve group at 2 weeks. Spheroid PD-MSCs exhibited a significantly higher efficiency of engraftment onto ovarian tissues at 2 weeks. The mRNA and protein expression levels of Nanos3, Nobox, and Lhx8 were also significantly increased in the Spheroid group compared with those in the NTx group at 1 and 2 weeks. These results suggest that PD-MSC transplantation can restore ovarian function in Ovx rats by increasing estrogen production and enhancing folliculogenesis-related gene expression levels and further indicate that spheroid-cultured PD-MSCs have enhanced therapeutic potential via increased engraftment efficiency. These findings improve our understanding of stem-cell-based therapies for reproductive systems and may suggest new avenues for developing efficient therapies using 3D cultivation systems.

The insulin resistance caused by impaired glucose metabolism induces ovarian dysfunction due to the central importance of glucose as a source of energy. However, the research on glucose metabolism in the ovaries is still lacking. The objectives of this study were to analyze the effect of PD-MSCs on glucose metabolism through IGFBP2–AMPK signaling and to investigate the correlation between glucose metabolism and ovarian function. Thioacetamide (TAA) was used to construct a rat injury model. PD-MSCs were transplanted into the tail vein (2 × 106) 8 weeks after the experiment started. The expression of the IGFBP2 gene and glucose metabolism factors (e.g., AMPK, GLUT4) was significantly increased in the PD-MSC group compared to the nontransplantation (NTx) group (* p < 0.05). The levels of follicular development markers and the sex hormones AMH, FSH, and E2 were also higher than those in the TAA group. Using ex vivo cocultivation, the mRNA and protein expression of IGFBP2, AMPK, and GLUT4 were significantly increased in the cocultivation with the PD-MSCs group and the recombinant protein-treated group (* p < 0.05). These findings suggest that the increased IGFBP2 levels by PD-MSCs play an important role in glucose metabolism and ovarian function through the IGFBP2–AMPK signaling pathway.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.

Diabetic retinopathy (DR) is a major cause of adult blindness and is characterized by progressive retinal vascular dysfunction and pathological angiogenesis. To establish a DR model, streptozotocin (STZ) was intraperitoneally injected into rats. After 8 weeks, naïve placenta-derived mesenchymal stem cells (PD-MSCs) or PEDF-overexpressing PD-MSCs (PD-MSCsPEDF) were intravitreally transplanted into the right eye for 4 weeks. Pathological neovascularization in DR is regulated by the balance between vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). In diabetic retinas, increased VEGF and decreased PEDF expression were reversed following PD-MSC transplantation. Notably, PD-MSCsPEDF treatment resulted in higher PEDF, and lower VEGF expression compared with naïve PD-MSCs, with similar expression patterns observed in the contralateral non-transplanted eyes. These findings indicate that engineering PD-MSCsPEDF enhances anti-angiogenic activity by modulating VEGF and PEDF balance, thereby alleviating vascular damage in STZ-induced diabetic retinas.

Lipid accumulation disrupts mitochondrial dynamics, leading to dysfunctional energy metabolism and increased oxidative stress. However, the relationship between mitochondrial dynamics and ovarian function in therapeutic contexts is still not fully elucidated. Therefore, the objective of this study was to demonstrate whether increased carnitine palmitoyltransferase 1A (CPT1A) expression induced by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in ovaries of a lipid toxicity-induced rat model by regulating lipid metabolism and mitochondrial dynamics. A rat model of injury was induced through intraperitoneal administration of thioacetamide (TAA) for 12 weeks. During the 8th week of induction, PD-MSCs (2 × 10 cells) were transplanted via the tail vein. Initially, we examined the engraftment of PD-MSCs. The inflammatory response (e.g., IL-6, TNFα) and apoptosis (e.g., LDH levels, TUNEL assay) were significantly increased in the non-transplanted (NTx) group compared to the normal group; however, they were significantly decreased in the transplanted (Tx) group compared to the NTx group (* < 0.05). Additionally, oxidative stress was attenuated through the regulation of mitochondrial dynamics, including the expression of DRP1, ATP5B, and PGC1α, in the Tx group compared to the NTx group (* < 0.05). In the NTx group, abnormally accumulated lipid droplets were observed due to dysfunctional mitochondria, whereas in the Tx group, the accumulation of lipid droplets and the expression of CPT1A were significantly comparable to those in the normal group (* < 0.05). The levels of the steroidogenesis markers (e.g., CYP11A1 and HSD3β1) were decreased in the NTx group compared to the normal group and increased in the Tx group compared to the NTx group (* < 0.05). The levels of sex hormone and follicular development were protected in the Tx group compared to the NTx group. Furthermore, cocultivation of PD-MSCs with etomoxir (CPT1A inhibitor)-treated primary theca cells increased the expression of steroidogenesis. In conclusion, PD-MSCs improve ovarian function in TAA-induced injury by reducing lipid accumulation and oxidative stress through the regulation of lipid metabolism and mitochondrial dynamics. The upregulation of CPT1A and related mitochondrial proteins contributes to enhanced steroidogenesis and restoration of ovarian homeostasis. These findings offer new insights into the application of stem cell therapies for reproductive medicine.

Background/Aims: Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration.Methods: We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCsPRL-1) in a bile duct ligationinduced rat injury model, focusing on their ability to regulate EMT.Results: PD-MSCsPRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCsPRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling. Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes.Conclusions: PRL-1 expression in PD-MSCsPRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition. These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.

Ovarian dysfunction resulting from metabolic or toxic injury is characterized by follicular depletion, stromal remodeling, oxidative stress, and endocrine dysregulation. Placenta-derived mesenchymal stem cells (PD-MSCs) have been proposed as a potential therapeutic approach due to their paracrine factors, including placental growth factor (PlGF). However, the pathways through which PD-MSCs exert protective effects on the ovary remain insufficiently defined. In this study, we examined whether PD-MSC transplantation ameliorates ovarian injury in a thioacetamide (TAA)-induced ovarian insufficiency model and explored the signaling events potentially associated with this response. Female rats were administered TAA for 12 weeks, and PD-MSCs were transplanted at week 8. We assessed ovarian morphology, fibrosis, oxidative stress markers, hormonal profiles, and follicle development. Complementary in vitro experiments using TAA-treated KGN granulosa-like cells were performed to investigate potential mechanistic associations. PD-MSC transplantation improved ovarian architecture, reduced collagen deposition, enhanced follicle growth, and mitigated oxidative stress. These changes were accompanied by increased PlGF expression and enhanced activation of fms-like tyrosine kinase-1 (Flt-1), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidant pathways. In vitro, PD-MSCs coculture similarly attenuated oxidative stress and partially improved mitochondrial membrane potential in damaged KGN cells. Together, these findings suggest that PD-MSCs ameliorate ovarian structural damage and oxidative stress in TAA-induced injury, potentially through paracrine mechanisms partly involving PlGF/Flt-1-associated antioxidant signaling. This work supports the therapeutic potential of PD-MSCs for metabolic or toxicant-induced ovarian insufficiency while underscoring the need for further studies to fully delineate the specific contribution of PlGF and its interaction with downstream antioxidant pathways.

Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.

Stem cell therapy is attracting attention in the field of regenerative medicine and is advancing rapidly. Many recent studies have applied stem cell therapy to treat reproductive system diseases; however, data are not yet available as to whether this therapy shows enhanced therapeutic effects. This paper analyzes recent preclinical studies on stem cell therapy for ovarian dysfunction in several types of animal models. Several clinical trials and pending projects are also discussed. This review will provide a background for developing stem cell therapies to enhance ovarian function.

Considering the characteristics of wind tunnel tests, a position measurement system that can minimize the effects on the flow of simulated wind must be established. In this study, a motion-capture camera was used to measure the displacement responses of structures in a wind tunnel test, and the applicability of the system was tested. A motion-capture system (MCS) could output 3D coordinates using two-dimensional image coordinates obtained from the camera. Furthermore, this remote sensing system had some flexibility regarding lab installation because of its ability to measure at relatively long distances from the target structures. In this study, we performed wind tunnel tests on a pylon specimen and compared the measured responses of the MCS with the displacements measured with a laser displacement sensor (LDS). The results of the comparison revealed that the time-history displacement measurements from the MCS slightly exceeded those of the LDS. In addition, we confirmed the measuring reliability of the MCS by identifying the dynamic properties (natural frequency, damping ratio, and mode shape) of the test specimen using system identification methods (frequency domain decomposition, FDD). By comparing the mode shape obtained using the aforementioned methods with that obtained using the LDS, we also confirmed that the MCS could construct a more accurate mode shape (bending-deflection mode shape) with the 3D measurements.