Complexity of enhancer networks predicts cell identity and disease genes revealed by single-cell multi-omics analysis.

Many enhancers exist as clusters in the genome and control cell identity and disease genes; however, the underlying mechanism remains largely unknown. Here, we introduce an algorithm, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. The complexity of enhancer networks is assessed by two metrics: the number of enhancers and the frequency of predicted enhancer interactions (PEIs) based on chromatin co-accessibility. We apply eNet algorithm to a human blood dataset and find cell identity and disease genes tend to be regulated by complex enhancer networks. The network hub enhancers (enhancers with frequent PEIs) are the most functionally important. Compared with super-enhancers, enhancer networks show better performance in predicting cell identity and disease genes. eNet is robust and widely applicable in various human or mouse tissues datasets. Thus, we propose a model of enhancer networks containing three modes: Simple, Multiple and Complex, which are distinguished by their complexity in regulating gene expression. Taken together, our work provides an unsupervised approach to simultaneously identify key cell identity and disease genes and explore the underlying regulatory relationships among enhancers in single cells.

Deciphering the endometrial niche of human thin endometrium at single-cell resolution.

Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling pathways as causes for the insufficient proliferation of the endometrium. Together, these data provide insight into therapeutic strategies for endometrial regeneration and growth to treat thin endometrium.

Biomimetic Dual-Network Collagen Fibers with Porous and Mechanical Cues Reconstruct Neural Stem Cell Niche via AKT/YAP Mechanotransduction after Spinal Cord Injury.

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.

Recent advances in the fabrication of pH-sensitive indicators films and their application for food quality evaluation.

Over a few decades, anthocyanin (ACN)-based colorimetric indicators in intelligent packaging systems have been widely used to monitor the freshness or spoilage of perishable food products. Most of the perishable food products are highly susceptible to enzymatic/microbial spoilage and produce several volatile or nonvolatile organic acid and nitrogenous compounds. As a result, the natural pH of fresh foods significantly changes. Fabrication of CAN-based colorimetric indicators in intelligent packaging systems is an advanced technique that monitors the freshness or spoilage of perishable foods based on the display of color variations at varying pH values. This study focuses on the advancement of pH-sensitive indicators and extraction of colorimetric indicators from commercially available natural sources. Moreover, the fabrication techniques and widespread industrial applications of such indicators have also been discussed. In addition, readers will get information about the color-changing and antioxidant mechanisms of ACN-based indicator films in food packaging.

Single-cell analysis reveals dynamic changes of neural cells in developing human spinal cord.

During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFR-expressing transitional glial cells exhibited a unique position-specific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.

Direct neuronal differentiation of neural stem cells for spinal cord injury repair.

Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary white matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.

Research progress on antimicrobial materials for food packaging.

Microbial contamination is an utmost cause of food spoilage. Antimicrobial agents are used to treat microbial diseases in food. They also serve food packaging industry, as they are used for the formation of antimicrobial packaging films which maintain the structure, texture, color, and nutrition value of food. Due to ever growing population, the demands of food are also rising. There is need to stop food wastage and to prevent spoilage. Most of the food is spoiled during harvesting, transportation, and distribution. This is a serious problem to overcome. Adding antibacterial agents is the most convenient way to reduce food spoilage and contamination. To support the characteristics and properties of antibacterial materials, different modifications are performed in the field of food packaging, which is one of the most demanding techniques for food preservation. This review will summarize the research about antimicrobial agents, with an emphasis on recent findings, to highlight the importance of new developments in this field. Concepts of antimicrobial packaging with a focus on antibiotics and antibacterial agents are discussed briefly in this review, along with the different types of food packaging and applications of antimicrobial packaging. Synthetic and natural antimicrobial materials are described. In summary, this article will explain the importance of antibacterial agents and their use in food packaging industry. Furthermore, readers will get good information about natural antibacterial polymers which were extensively used in past few decades. Subsequently, different innovations should be done to control food spoilage and wastage to ensure food safety. Food packaging is a sole element that helps to provide safe and secure food for all.

Electrospun nanofibers food packaging: trends and applications in food systems.

Food safety is a bottleneck problem. In order to provide information about advanced and unique food packaging technique, this study summarized the advancements of electrospinning technique. Food packaging is a multidisciplinary area involving food science, food engineering, food chemistry, and food microbiology, and the interest in maintaining the freshness and quality of foods has grown considerably. For this purpose, electrospinning technology has gained much attention due to its unique functions and superior processing. Sudden advancements of electrospinning have been rapidly incorporated into research. This review summarized some latest information about food packaging and different materials used for the packaging of various foods such as fruits, vegetables, meat, and processed items. Also, the use of electrospinning and materials used for the formation of nanofibers are discussed in detail. However, in food industry, the application of electrospun nanofibers is still in its infancy. In this study, different parameters, structures of nanofibers, features and fundamental properties are described briefly, while polymers fabricated through electrospinning with advances in food packaging films are described in detail. Moreover, this comprehensive review focuses on the polymers used for the electrospinning of nanofibers as packaging films and their applications for variety of foods. This will be a valuable source of information for researchers studying various polymers for electrospinning for application in the food packaging industry.

Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury.

Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.

Characterization and preliminary safety evaluation of nano-SiO2 isolated from instant coffee.

The physiological and toxicological evaluation of nano-silicon dioxide (nano-SiO2) particles in food is important for ensuring food safety. In this study, nano-SiO2 particles isolated from five brands of instant coffee, were structurally characterized using transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, dynamic light scattering, and zeta potential analyses. Their toxicity was assessed by measuring cell viability, membrane integrity, and reactive oxygen species (ROS) levels in model gastrointestinal cells (GES-1 and Caco-2). Additionally, mortality, deformity rate, heart rate and death of whole zebra fish embryos were measured. The five types of nano-SiO2 samples comprised amorphous particles with a purity of approximately 99%, which met the food additive standard. Considering that the original particle size ranged from 10 to 50 nm, the samples were classified as nano-SiO2 food additives. Nano-SiO2 did not significantly impact the activity of GES-1 or Caco-2 cells, and no significant cell membrane damage was observed (Caco-2 cells exhibited mild micro damage); however, a slight increase in intracellular RPS levels was detected. Moreover, nano-SiO2 was found to cause head deformity, pericardial edema, yolk sac edema and tail bending. Collectively, the results show that nano-SiO2 time- and dose-dependently affects GES-1 and Caco-2 cell viability, as well as the mortality, heart rate, and abnormality rate of zebra fish embryos. Specifically, a high concentration (≥ 200 µg/mL) and long exposure time (≥ 48 h) of food additive nano-SiO2 affected GES-1, Caco-2 cells, and the gastrointestinal tract in zebra fish embryos.

Electrospun antibacterial poly(vinyl alcohol)/Ag nanoparticles membrane grafted with 3,3',4,4'-benzophenone tetracarboxylic acid for efficient air filtration.

In this study, poly(vinyl alcohol) (PVA) membranes containing Ag nanoparticles (AgNPs) were prepared by electrospinning and grafted copolymerization with 3,3',4,4'-benzophenone tetracarboxylic acid (BPTA) to provide better mechanical properties, lower water vapor transmittance, and higher antibacterial activity (against Staphylococcus aureus and Escherichia coli) than the PVA/AgNPs membrane. The PVA/AgNPs/BPTA membrane showed higher antibacterial activity than the other membranes, and it produced inhibition zones with diameters of 18.12 ± 0.08 and 16.41 ± 0.05 mm against S. aureus and E. coli, respectively. The PVA/AgNPs/BPTA membrane was found to be capable of promoting reactive oxygen species (ROS) formation under both light and dark conditions. Cycling experiments performed following ROS quenching showed that the best-performing composite membrane retained >70% of its original OH⋅ radical and H2O2 charging capacity after seven cycles. In the filtration test, the electrospun nanofibrous membranes showed high filtration efficiencies of 99.98% for sodium chloride (NaCl). In addition, these membranes maintained a relatively low pressure drop of 168 Pa with a basis weight of 2.1 g m-2. Thus, the PVA/AgNPs/BPTA membrane was concluded to be a promising medical protective material offering the benefits of structural stability and reusability.

In situ Synthesis of Biomimetic Silica Nanofibrous Aerogels with Temperature-Invariant Superelasticity over One Million Compressions.

Resilient and compressible three-dimensional nanomaterials comprising polymers, carbon, and metals have been prepared in diverse forms. However, the creation of thermostable elastic ceramic aerogels remains an enormous challenge. We demonstrate an in situ synthesis strategy to develop biomimetic silica nanofibrous (SNF) aerogels with superelasticity by integrating flexible electrospun silica nanofibers and rubber-like Si-O-Si bonding networks. The stable bonding structure among nanofibers is in situ constructed along with a fibrous freeze-shaping process. The resultant SNF aerogels exhibit integrated properties of ultralow density (>0.25 mg cm-3 ), temperature-invariant superelasticity up to 1100 °C, and robust fatigue resistance over one million compressions. The ceramic nature also endows the aerogels with fire resistance and ultralow thermal conductivity. The successful synthesis of the SNF aerogels opens new pathways for the design of superelastic ceramic aerogels in a structurally adaptive and scalable form.

Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full-thickness injury.

Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full-thickness injury. One hundred and twenty four female Sprague-Dawley rats were assigned to three groups, including a sham-operated group (n = 34 uterine horns), a PBS/collagen group (n = 90 uterine horns), and a LIF/collagen group (n = 124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8, or 12 weeks after the surgery. The results showed that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full-thickness defect in excision sites (p < 0.001 vs PBS/collagen). Eight weeks after the surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in the PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a-smooth muscle actin (a-SMA)-positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down-regulated the pro-inflammatory cytokine IL-12 expression while up-regulating the anti-inflammatory cytokine IL-10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.

Preparation of SiO2-MnFe2O4 Composites via One-Pot Hydrothermal Synthesis Method and Microwave Absorption Investigation in S-Band.

MnFe2O4 NPs are successfully decorated on the surface of SiO2 sheets to form the SiO2-MnFe2O4 composite via one-pot hydrothermal synthesis method. The phase identification, morphology, crystal structure, distribution of elements, and microwave absorbing properties in S-band (1.55~3.4 GHz) of the as-prepared composite were investigated by XRD, SEM, TEM, and Vector Network Analyzer (VNA) respectively. Compared with the pure MnFe2O4 NPs, the as-prepared SiO2-MnFe2O4 composite exhibits enhanced microwave absorption performance in this frequency band due to the strong eddy current loss, better impedance matching, excellent attenuation characteristic, and multiple Debye relaxation processes. The maximum reflection loss of -14.87 dB at 2.25 GHz with a broader -10 dB bandwidth over the frequency range of 1.67~2.9 GHz (1.23 GHz) can be obtained at the thickness of 4 mm. Most importantly, the preparation method used here is relatively simple, hence such composite can be served as a potential candidate for effective microwave absorption in S-band.

[Advances in the study of ovarian dysfunction with aging].

Societal changes regarding the role of women have significant impacts on women's willingness and the timing of childbearing. Ovarian reserve in woman typically begins to decline at the age of 35, and it is primarily characterized by a reduction in the number of ovarian follicles and a decline in oocyte quality. The clinical diagnosis of ovarian insufficiency relies on multiple variables including changes of follicle stimulating hormone (FSH), serum anti-Müllerian hormone (AMH), inhibin B, antral follicle count, menstruation and age. It is proven that ovarian cells demonstrate dysfunction associated with aging including mitochondrial dysfunction, telomere shortening, impaired DNA repair, epigenetic changes and metabolic/energetic disorders. In this review, we introduce the clinical diagnosis and management of ovarian insufficiency. We mainly discuss the molecular mechanism and potential interventions. We are optimistic that this information and knowledge will inform the important decisions for women and society regarding childbearing.

Graphene Oxide Incorporated PLGA Nanofibrous Scaffold for Solid Phase Gene Delivery into Mesenchymal Stem Cells.

Delivery of functional genes into stem cells shows great application prospect in DNA-based tissue engineering. However, comparing with epithelial cells and cancer cells, stem cells usually exhibit low gene transfection efficiency. To enhance the transfection efficiency, non-viral gene delivery in combination with biomaterial scaffolds, has raised increasing interests from researchers in tissue engineering. Nanofibers fabricated by electrospinning technique mimicking extracellular matrix (ECM) are widely used in tissue engineering applications. In addition, graphene oxide (GO) with ultrahigh specific surface area and ultra-strong adsorption capability, is an ideal candidate for gene delivery. In this work, polyethylenimine (PEI)/plasmid DNA-GO/poly(D,L-lactic-co-glycolic acid) (PLGA) scaffold was developed as a substrate for solid phase gene delivery and a tissue engineering substrate for stem cells growth and differentiation. In order to improve the transfection efficiency of stem cells, PEI/pDNA complexes were immobilized at the surface of electropun GO incorporated PLGA nanofibrous mat. Human embryonic kidney 293 cells and human umbilical cord derived mesenchymal stem cells cultured on PEI/pDNA-GO/PLGA scaffold showed significantly higher green fluorescent protein (GFP) expression than PEI/pGFP in the medium. These findings demonstrated that solid phase gene delivery using PEI/pDNA-GO/PLGA significantly enhanced the gene transfection efficiency, and may find potential application of gene therapy and regeneration medicine.

Restoration of mandibular bone defects with demineralized bone matrix combined with three-dimensional cultured bone marrow-derived mesenchymal stem cells in minipig models.

Mandibular defects, caused by congenital, pathological or iatrogenic insults, can significantly affect patient quality of life. The reconstruction of mandible has recently gained the interest of clinical and tissue engineering researchers. The purpose of this study was to evaluate the effectiveness of three-dimensional (3-D) cultured autologous grafts prepared using bone marrow-derived mesenchymal stem cells (BMSCs) combined with demineralized bone matrix (DBM) scaffolds for the restoration of mandibular defects. Cylindrical defects were created in the mandibular body of minipigs and filled with 3D-cultured BMSCs/DBM autografts, 2D-cultured BMSCs/DBM autografts, DBM material (without cells), or were left unfilled (blank). Using computed tomographic (CT) imaging and histological staining, we found that treatment of mandibular defects using 3-D cultured BMSCs/DBM autografts offered improvements in bone formation over both 2-D cultured autografts and cell-free DBM scaffolds. We found increased osteoid formation in 3D and 2D cultures, with more osteogenic cells present in the 3D constructs. We suggest that 3-D cultured homograft BMSCs combined with DBM scaffolds represents a new strategy for bone reconstruction, with potential future clinical applicability.

An effective delivery vehicle of demineralized bone matrix incorporated with engineered collagen-binding human bone morphogenetic protein-2 to accelerate spinal fusion at low dose.

The aim of this study was to investigate the feasibility and efficacy of a new delivery matrix using demineralized bone matrix (DBM) incorporated with collagen-binding bone morphogenetic protein-2 (CBD-BMP-2) in the rat inter-transverse spinal fusion model. Sixty rats undergoing posterolateral (inter-transverse) spinal fusion were divided into 3 groups according to the fusion materials containing different components (n = 20 per group). Group A were implanted with DBM, Group B with combination of DBM and BMP-2 and Group C with combination of DBM and CBD-BMP-2. After surgery, the spinal fusion of all the rats was assessed by plain radiography, CT + 3D reconstruction, manual palpation and histological evaluation. Significant difference was found in terms of solid fusion rate among the three groups, with 95% in Group C, 65% in Group B and 0% in Group A (P < 0.001). Compared with Groups B and A, new bone formation was observed earlier and was obvious larger, trabecular bone microarchitecture assessment was better and bone mineral density was statistically larger in Group C. In addition, more newly woven bone and osteocytes were shown by histological evaluation in Group C at 4 weeks post-operation. The present study showed CBD domain could help BMP-2 to improve the efficiency of posterolateral spinal fusion. DBM scaffold activated by collagen-binding BMP-2 was a feasible and promising bone repair vehicle. The present study showed better results in terms of plain radiography, CT + 3D reconstruction, manual palpation and histological evaluation in the rat inter-transverse spinal fusion model using DBM+CBD-BMP-2, compared with DBM+BMP-2 and DBM alone, indicating DBM scaffold activated by collagen-binding BMP-2 was a feasible and promising bone repair vehicle.

Radially Aligned Electrospun Fibers with Continuous Gradient of SDF1α for the Guidance of Neural Stem Cells.

Repair of spinal cord injury will require enhanced recruitment of endogenous neural stem cells (NSCs) from the central canal region to the lesion site to reestablish neural connectivity. The strategy toward this goal is to provide directional cues, e.g., alignment topography and biological gradients from the rostral and caudal ends toward the center. This study demonstrates a facile method for fabrication of continuous gradients of stromal-cell-derived factor-1α (SDF1α) embedded in the radially aligned electrospun collagen/poly (ε-caprolactone) mats. Gradients can be readily produced in a controllable and reproducible fashion by adjusting the collection time and collector size during electrospinning. To get a long-term gradient, the SDF1α is fused with a unique peptide of collagen-binding domain (CBD), which can bind to collagen specifically. Aligned CBD-SDF1α gradients show stable, sustained, and gradual release during 7 d. Further, the effect of aligned CBD-SDF1α gradients on the guidance of NSCs is investigated. It is found that the CBD-SDF1α gradient scaffolds direct and enhance NSC migration from the periphery to the center along the aligned electrospun fibers. Taken together, the tubular conduits based on radially aligned electrospun fibers with continuous SDF1α gradient show great potential for guiding nerve regeneration.

Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency.

STUDY QUESTION: Does the transplantation of adipose-derived stem cells (ADSCs) on soluble collagen scaffolds (collagen/ADSCs) have better therapeutic effect than transplantation of ADSCs alone, to treat premature ovarian insufficiency (POI) in a rat model induced by Tripterygium Glycosides (TG)? SUMMARY ANSWER: The transplantation of collagen/ADSCs increased the short-term retention of ADSCs in ovaries and contributed to long-term restoration of ovarian function, as well as the fertility of rats with TG-induced ovarian damage. WHAT IS KNOWN ALREADY: About 50% of young women in China, who have been treated with TG, have subsequently developed ovarian insufficiency. Rats exhibit similar symptoms to these patients when given an equivalent dose of TG. Transplantation of ADSCs improves ovarian function impaired by chemotherapy in rodent models. STUDY DESIGN, SIZE, DURATION: After the administration of TG, 54 POI model rats were randomly assigned to 4 groups: phosphate buffered saline (PBS) ( ITALIC! n = 14), collagen ( ITALIC! n = 11), ADSCs ( ITALIC! n = 16) and collagen/ADSCs ( ITALIC! n = 13). Seventeen normal rats were assigned as control group. The retention of ADSCs in ovaries was confirmed immediately or at 3, 7, 14 and 28 days after transplantation ( ITALIC! n = 9). Four weeks after transplantation, ovarian function was evaluated from estrous cycle, estradiol level, the follicle number, granulosa cell proliferation and a fertility test. PARTICIPANTS/MATERIALS, SETTING, METHODS: To establish the POI model, rats were administered 60 mg TG/kg/day intragastrically for 50 days. The estrous cycles were assessed by vaginal smear. The concentration of plasma estradiol in diestrus stage was measured using a radioimmunoassay kit. Disordered estrous cycles and low serum estradiol levels indicated the successful establishment of the POI model. Four types of suspensions (PBS, collagen, ADSCs and collagen/ADSCs) were transplanted directly into the core of the ovaries. The short-term retention of ADSCs in ovaries was evaluated by small-animal positron emission tomography images immediately after transplantation of (18)F-Fluorodeoxyglucose ((18)F-FDG) labeled ADSCs. The long-term retention of ADSCs in ovaries was observed by immunohistochemistry after transplantation of green fluorescent protein (GFP)-labeled ADSCs. Serial sections of ovaries were prepared for histological analysis, follicle counting, and immunohistochemistry for Ki67 and Cleaved-Caspase-3. For the assessment of fertility, rats were mated with proven fertile male rats for 10 days. MAIN RESULTS AND THE ROLE OF CHANCE: The (18)F-FDG signal decreased more slowly in ovaries injected with collagen/ADSCs than in ovaries with injected with ADSCs alone. Significantly more GFP-positive cells were observed in ovaries injected with collagen/GFP-ADSCs than in ovaries injected with GFP-ADSCs alone up to 14 days after the injection. However, in both groups very few GFP-positive cells were present at 4 weeks after transplantation. The collagen/ADSCs and ADSCs groups both showed better estrous cycle recovery than the PBS and collagen groups. The estradiol (E2) level in the collagen/ADSCs group was significantly increased compared with that of the PBS group ( ITALIC! P < 0.05). The number of antral follicles in the collagen/ADSCs group and the ADSCs group significantly increased compared with the PBS group ( ITALIC! P < 0.05). The granulosa cell proliferation in the collagen/ADSCs group was better than in the PBS group ( ITALIC! P < 0.01). The mating rates of the collagen/ADSCs group (88.9%) and the ADSCs group (90.9%) were higher than that of PBS group (60%, ITALIC! P < 0.05). The pregnancy rates of the collagen/ADSCs group (77.8%) and the ADSCs group (72.7%) were higher than the PBS group (50%, ITALIC! P < 0.05). LIMITATIONS, REASONS FOR CAUTION: We chose ADSCs for their accessibility, convenience and safety. We did not use other cells or materials for POI treatments to show that the collagen/ADSCs are the most promising materials. WIDER IMPLICATIONS OF THE FINDINGS: Soluble collagen scaffolds may be useful in stem cells transplantation therapy for POI. STUDY FUNDING/COMPETING INTERESTS: This work is supported by grants from the 'Strategic Priority Research Program' of the Chinese Academy of Sciences (XDA01030000); Maternal-Fetal Medicine from Jiangsu Province Health Department of China (XK2011027); Clinical Center of Obstetric, Gynecologic and Genetic Diseases, Nanjing Health Department of Jiangsu Province, China; Fundamental Research Funds for the Central Universities (20620140652). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER: Not applicable.