Premature ovarian failure (POF), a condition influenced by genetic and immune factors, remains incurable despite years of intensive research and significant efforts. This persisting challenge underscores the urgency to address this escalating health concern. Fortunately, stem cell regenerative medicine has emerged as a promising avenue for developing therapeutic strategies and innovative treatments for POF. Bibliometric analysis, renowned for its objectivity, systematic approach, and comprehensive coverage of a given field, has yet to be applied to the study of stem cell research in POF. This study used CiteSpace software to assess contributions and co-occurrence relationships among various countries/regions, institutes, journals, and authors. This approach also allowed us to identify research hotspots and promising future trends within this field. Additionally, we generated visualizing maps utilizing the Web of Science Core Collection (WOSCC) and PubMed publications. By providing valuable information and references, we aim to enhance the understanding of the challenges involved in translating stem cell regeneration into clinical therapeutic potential for POF. Furthermore, our analysis and findings guide researchers and clinicians, facilitating future collaborative research and clinical intervention efforts.

Stem cell transplantation has emerged as a promising avenue in regenerative medicine, potentially facilitating tissue repair in degenerative diseases and injuries. This review comprehensively examines recent developments and challenges in stem cell transplantation. It explores the identification and isolation of various stem cell types, including embryonic, induced pluripotent, and adult stem cells derived from multiple sources. Additionally, the review highlights the tissue-specific applications of these stem cells, focusing on bone and cartilage regeneration, treatment of neurological disorders, and management of hematological conditions. Future advancements and effective resolution of current challenges will be crucial in fully realizing the potential of stem cell transplantation in regenerative medicine. With responsible and ethical practices, the field can potentially transform disease and injury treatment, ultimately improving the quality of life for countless individuals.

Erectile dysfunction (ED) is a common disorder in men and lacks effective treatment. Stem cell (SC) possess the potential in self-renewal and multi-directional differentiation, and secrete a variety of active substances. Stem cell therapy, as a promising option for the treatment of ED, is a focus in regenerative medicine research. However, the effect of stem cell therapy alone on ED is limited due to the complexity of the condition and the limitations of SC. Gene modification can enhance the performance of SC in multiple aspects and play the role of targeted genes, and therefore can better improve ED and its related pathological changes than SC therapy alone. In recent years, gene-modified stem cell therapy has become a hotspot in andrological research. This review summarizes the advances in the studies of gene-modified SC in the treatment of ED, aiming to provide some ideas for further research.

The aim of the present study was to examine the efficacy of the modified post-transplant cyclophosphamide (PTCy) regimen, which involved reducing the Cy dose to 40 mg on days +3 and +4, in patients with severe aplastic anemia (SAA) subjected to unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT). For this purpose, a prospective single-center trial was conducted and the clinical outcomes were collected from 30 patients with SAA treated with the modified PTCy regimen for URD HSCT. The median time to neutrophil and platelet engraftment was 13 days (range, 11 to 16) and 12 days (range, 5 to 33), respectively. The cumulative incidence of neutrophil and platelet engraftment was 93.1±0.3% and 96.6±0.2%, respectively. The 2-year overall survival (OS) was 97% [95% confidence interval (CI): 90%-100%] and 2-year graft-versus-host disease (GVHD) and rejection-free survival (GRFS) was 93% (95% CI: 85%-100%). The incidence rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were 13.8±0.4% and 10.3±0.3%, respectively, and no patients developed grade III-IV aGVHD. However, only one patient developed a moderate extensive cGVHD. The incidence of reconstitution varies among different subsets of immune cells after URD HSCT. Natural killer (NK) cells first recover, followed by CD8+ T and CD19+ B cells, and finally CD4+ T cells. In conclusion, the present study demonstrates that the modified PTCy regimen, with a reduced dose of 40mg on days +3 and +4, may be an effective regimen for URD HSCT in patients with SAA and reduce the occurrence of the GVHD.

BACKGROUND: Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period.
METHODS: To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation.
RESULTS: In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation.
CONCLUSIONS: The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.

In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.

Premature ovarian insufficiency (POI) is defined as onset of menopause characterized by amenorrhea, hypergonadotropism, and hypoestrogenism, before the age of 40 years. The POI is increasing, which seriously affects the quality of patients\' life. Due to its diversity of pathogenic factors, complex pathogenesis and limited treatment methods, the search for finding effective treatment of POI has become a hotspot. Stem cells are characterized by the ability of self-renewal and differentiation and play an important role in the regeneration of injured tissues, which is therapy is expected to be used in the treatment of POI. The aim of this review is to summarize the pathogenic mechanisms and the research progress of POI treatment with stem cells from different sources.

Electrical stimulation holds promise for enhancing neuronal differentiation of neural stem cells to treat traumatic brain injury. However, once the stem cells leave the stimulating material and migrate post transplantation, electrical stimulation on them is diminished. Here, we wrap the stem cells with wireless electrical nanopatches, the conductive graphene nanosheets. Under electromagnetic induction, electrical stimulation can thus be applied in-situ to individual nanopatch-wrapped stem cells on demand, stimulating their neuronal differentiation through a MAPK/ERK signaling pathway. Consequently, 41% of the nanopatch-wrapped stem cells differentiate into functional neurons in 5 days, as opposed to only 16.3% of the unwrapped ones. The brain injury male mice implanted with the nanopatch-wrapped stem cells and exposed to a rotating magnetic field 30 min/day exhibit significant recovery of brain tissues, behaviors, and cognitions, within 28 days. This study opens up an avenue to individualized electrical stimulation of transplanted stem cells for treating neurodegenerative diseases.

BACKGROUND: Full-thickness skin grafts are widely used in plastic and reconstructive surgery. The main limitation of skin grafting is the poor textural durability and associated contracture, which often needs further corrective surgery. Excessive inflammation is the main reason for skin graft contractions, which involve overactivation of myofibroblasts. These problems have prompted the development of new therapeutic approaches, including macrophage polarization modulation and stem cell-based therapies. Currently, adipose-derived stem cells (ASCs) have shown promise in promoting skin grafts survival and regulating macrophage phenotypes. However, the roles of ASCs on macrophages in decreasing skin grafts contraction remain unknown.
METHODS: Rat adipose-derived stem cells (rASCs) were isolated from rat inguinal adipose tissues. Full-thickness skin graft model was constructed on male rats divided into control group and rASCs treatment group. Skin graft was assessed for concentration, elasticity modulus and stiffness. Rat bone marrow-derived macrophages (rBMDMs) were isolated from rat femurs, and subsequent RT-qPCR and coculture assays were carried out to explore the cellular mechanisms. Immunohistochemical and immunofluorescence staining were used to verify mechanisms in vivo.
RESULTS: In vivo results showed that after injection of ASCs, improved texture, increased survival and inhibited contraction of skin grafts were seen. Vascularization was also improved as illustrated by laser perfusion image and vascular endothelial growth factor (VEGF) concentration. Histological analysis revealed that ASCs injection significantly reduced expression of pro-inflammatory cytokines (TNF-a, IL-1β) and increased expression of anti-inflammatory (IL-10) and pro-healing cytokines (IGF-1). At cellular level, after co-culturing with rASCs, rat bone marrow derived macrophages (rBMDMs) favored M2 polarization even under inflammatory stimulus.
CONCLUSIONS: ASCs treatment enhanced vascularization via angiogenic cytokines secretion and alleviated inflammatory environment in skin grafts by driving M2 macrophages polarization, which improved survival and decreased skin grafts contraction. Our work showed that ASCs transplantation can be harnessed to enhance therapeutic efficacy of skin grafting in cutaneous defects treatment.

Rabbit antithymocyte globulin (rATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent graft failure and severe graft-versus-host disease (GVHD). We developed a rATG-targeted dosing strategy based on the optimal areas under the concentration-time curve (AUC) of active rATG. This study compared the outcomes of the optimal AUC arm with nonoptimal AUC arm to assess the effect of the rATG-targeted dosing strategy. Eighty patients (median age: 32 years) with hematological malignancies who received their first haplo-PBSCT were enrolled successively. With rATG-targeted dosing, the AUC values of 60 patients (75%, optimal AUC arm) fell within the optimal range (100-148.5 UE/mL/day) and 20 fell beyond this range (nonoptimal AUC arm). In the historical control group of 102 haplo-PBSCT patients who received a fixed dose of rATG (10 mg/kg), less patients fell within the optimal range (57.8%, P = .016). Looking at the nonoptimal AUC arms in both groups, lower cumulative incidence of CMV was noted in the targeted dosing group compared with the historical control group(50.0%, 95% CI, 30.8%-72.9% versus 81.4%, 95% CI, 68.6%-91.3%; P = .004). The cumulative incidences of EBV, relapse, overall survival and disease-free survival tended to be superior in the nonoptimal AUC arm in the targeted dosing group compared with the historical control. In the targeted dosing group, the cumulative incidence of cytomegalovirus (CMV) reactivation on day +180 tended to be lower in the optimal AUC arm (30.0%, 95% CI, 20.1%-43.3%) compared with the nonoptimal AUC arm (50.0%, 95% CI, 30.8%-72.9%, P = .199) without statistical difference. There were no significant differences of acute or chronic GVHD, relapse, nonrelapse mortality, overall survival, disease-free survival or lymphocyte reconstitution between the two arms. In conclusion, the rATG-targeted dosing strategy made the exposure of active rATG in more patients with the optimal AUC range. Even patients who fell beyond this range would still benefit from the strategy.