Premature ovarian failure (POF) is one of the principal causes of female infertility, and although its causes are complex and diverse, autoimmune deficiency may be involved. Human umbilical cord mesenchymal stem cells (UCMSCs) can be used for tissue regeneration and repair. Therefore, the present study was designed to determine the role of UCMSCs in immune factor-induced POF in rats. In this study, different concentrations of UCMSCs were injected into induced POF rats. Ovarian functions were examined by evaluating the estrus cycle, follicular morphology, hormonal secretion, and the proliferation and apoptosis of granulosa cells. Our results showed that the estrus cycle of rats returned to normal and follicular development was significantly improved after transplantation of UCMSCs. In addition, serum concentrations of 17-estradiol (E2), progesterone (P4), and anti-Müllerian hormone (AMH) increased significantly with treatment. Transplantation of UCMSCs also reduced the apoptosis of granulosa cells and promoted the proliferation of granulosa cells. All of these improvements were dose dependent. Furthermore, the results of related gene expression showed that transplanted human UCMSCs upregulated the expression of Bcl-2, AMH, and FSHR in the ovary of POF rats and downregulated the expression of caspase-3. These results further validated the potential mechanisms of promoting the release of cell growth factors and enhancing tissue regeneration and provide a theoretical basis for the clinical application of stem cells in the treatment of premature ovarian failure.

Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions. They have proven to potentially take up and process tumor-associated antigens (TAAs). In this regard, researchers have developed strategies such as genetically engineered or TAA-pulsed DC vaccines; these manipulated DCs have shown significant outcomes in clinical and preclinical models. Here, we review DC classification and address how DCs are skewed into an immunosuppressive phenotype in cancer patients. Additionally, we present the advancements in DCs as a platform for cancer immunotherapy, emphasizing the technologies used for in vivo targeting of endogenous DCs, ex vivo generated vaccines from peripheral blood monocytes, and induced pluripotent stem cell-derived DCs (iPSC-DCs) to boost antitumoral immunity.

Objective: This study explored the underlying therapeutic mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and determined the optimal administration time windows and dose-effect relationship.Methods: The levels of SDF-1α, IL-10, IL-6, TNF-α, BDNF, IL-1β, and VEGF-A factors in serum and brain tissue lysate were measured by ELISA. The pathological status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. The balance beam, forelimb muscle strength, and limb placement were tested on MCAO rats at different time points and doses. The infarct area of the rat brain tissues was measured at the end of the experiment.Results: The hUCMSC treatment during the acute phase of MCAO significantly reduced the secretion of IL-6, TNF-α, IL-1β but increased IL-10 in serum, and the levels of SDF-α and BDNF in serum and brain tissues lysate were also increased. The pathological results showed that there were more neurons in the treatment group compared to the model group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN was relatively higher than that in the model group. The d4 and d7 treatment significantly improves the motor function, promotes the recovery of forelimb muscle strength, increases the forelimb placement rate and reduces the scope of cerebral infarction, but the d14 treatment group has less therapeutic effect compared to the d4 and d7 treatment. The 2×10⁷/kg treatment showed the best therapeutic effect, followed by the 1×10⁷/kg treatment, and the worst is 0.5×10⁷/kg treatment from the test of balance beam, forelimb muscle strength, limb placement and the infarct area of the rat brain tissues.Conclusion: The hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, and promote the repair of brain tissue structure and function. Early intervention by injecting high-dose of hUCMSCs can significantly improve the recovery of neurological/motor function and reduce the size of cerebral infarction in rats.

Macrophages (Mϕs) play an essential role in maintaining body homeostasis. They perform dual functions produced by different subtypes. Mϕs not only fight against pathogens and foreign bodies such as bacteria or cancer cells but also participate in healing and repairing damaged tissue since they maintain both proinflammatory and anti-inflammatory effects sequentially. Tumors possess the ability to polarize Mϕs from proinflammatory M1 subtype to anti-inflammatory M2-like Mϕs called tumor-associated macrophages, which, in turn, help the tumors to acquire cancer hallmarks. Consequently, this polarization allows tumors to grow and spread. In this light, Mϕs have been a subject of intense study, and researchers have developed protocols to derive different Mϕs subtypes either as a new state-of-the-art therapeutic approach or to understand the cross-talk between cancer and Mϕs. In this review, we present the use of Mϕs in adoptive immunotherapy for cancer, illustrate the reciprocating interplay between cancer and Mϕs, and the resulting structural and functional change on both cell types. Furthermore, we summarize the recent cutting-edge approaches of using Mϕs in cancer immunotherapy.

Introduction: Doxorubicin (DOX) is a highly effective anti-cancer drug, but its clinical applications are limited by its cardiotoxicity. The mechanisms underlying DOX-induced cardiotoxicity (DIC) remain incompletely understood. Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) offer an advanced platform for investigating DIC, as they accurately recapitulate human cardiac physiology and pathology. However, the roles and mechanisms of DIC in hiPSC-CMs and hESC-CMs, especially regarding autophagy dynamics and regulation, are still not well-defined. Methods: Cell viability, apoptosis, reactive oxygen species production, and DNA damage were assessed. Autophagy was evaluated by transmission electron microscope, LC3-II/LC3-I ratio, and autophagy flux assays. The role of autophagy and mTOR signaling was investigated using 3-methyladenine (3-MA) and rapamycin (RAPA), respectively. Results: DOX reduced cell viability and induced apoptosis in hiPSC-CMs and hESC-CMs. Additionally, DOX caused an increase in reactive oxygen species production and DNA damage. Furthermore, DOX significantly upregulated autophagy, confirmed by the accumulation of autophagosomes and autolysosomes, and an increase in the LC3-II/LC3-I ratio. Autophagy flux assays showed that DOX induced autophagy in a time-dependent manner. The autophagy mediated by DOX was partially attenuated by 3-MA. Moreover, this activation was due to mTOR signaling inhibition. The downregulation of mTOR signaling by RAPA increased cell death of hESC-CMs. Interestingly, minor variations in injury severity and cellular sensitivity were observed between these two models. Conclusion: Our study uncovered the multifaceted effects of DOX on hiPSC-CMs and hESC-CMs, revealing a shared mechanism in which DOX enhances autophagy via inhibition of the mTOR signaling pathway. These findings reveal key insights into DIC pathogenesis and suggest that autophagy modulation may be a promising therapeutic strategy.