scholarly journals Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis

Theranostics ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 1607-1623 ◽  
Author(s):  
Chun-Yuan Chen ◽  
Shan-Shan Rao ◽  
Lu Ren ◽  
Xiong-Ke Hu ◽  
Yi-Juan Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Urine ◽  
Wound Repair ◽  
Diabetic Wound

Graphene Oxide Accelerate Diabetic Wound Repair by Inhibiting Apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 Pathway

2021 ◽  
Author(s):  
Zhe Ji ◽  
Feifei Chen ◽  
Shuai Yang ◽  
Caiqi Shen ◽  
Hanxiao Wei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Repair ◽  
Target Gene ◽  
Diabetic Wound ◽  
Mirna Sponge ◽  
Downstream Signaling ◽  
Proliferation And Differentiation ◽  
Rna Immunoprecipitation ◽  
Auxiliary Material ◽  
Diabetic Wounds

Abstract BackgroundGraphene oxide (GO) has been proven in many studies to promote the proliferation and differentiation of a variety of stem cells, but its effect on the apoptosis of adipose-derived mesenchymal stem cells (Ad-MSCs) is still unclear. Apoptosis is one of the most important factors in the treatment of diabetic wounds by stem cells. Therefore, we explored its therapeutic effect on diabetic wounds by studying the effect of GO on the apoptosis of Ad-MSCs.MethodsqRT-PCR was used to detect the expression of lncRNAs, miRNAs and mRNAs in Ad-MSCs. RNA immunoprecipitation (RIP), RNA pull-down and luciferase assays were used to detect the interaction of the specific lncRNA, miRNA and mRNA. The effects of Linc00324 on Ad-MSCs cells apoptosis were explored by flow cytometer, TUNEL assay and Western blot. Diabetic wound was established to explore the function of Linc00324 on Ad-MSCs repairing ability in vivo.ResultsGO inhibited the apoptosis of Ad-MSCs caused by high glucose, and Linc00324 was one of the factors contributing to its effect. In terms of mechanism, RIP and RNA-Pull-down confirmed Linc00324 could directly interact with miR-7977, and then acted as a miRNA sponge to regulate the expression of miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. ConclusionsOverall, this study highlights that GO maybe a superior auxiliary material for Ad-MSCs to repair diabetic wounds via Linc00324/miR-7977/STK4 pathway.

Healing of Full-Thickness Wounds Using Platelet-Rich Fibrin Seeded with Adipose Stem Cells in a Diabetic Mouse Model

2020 ◽  
Vol 10 (3) ◽  
pp. 315-322
Author(s):  
Yanping Guo ◽  
Jing Liu ◽  
Plastic Surgery Department, Nanjing Medical U ◽  
Qiang Li ◽  
Department of Ear Reconstruction, Plastic Sur ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Laser Scanning ◽  
Wound Repair ◽  
Subcutaneous Fat ◽  
Cell Activity ◽  
Therapeutic Effects ◽  
Diabetic Wound ◽  
Platelet Rich Fibrin ◽  
Diabetic Wounds

Diabetic wounds are refractory to spontaneous healing and treatment regimes due to their detrimental nature. Adipose derived stem cells (ASCs) hold great potential in stem cell-based therapies. However, insufficient cell activity and survival after transplantation dramatically reduce the therapeutic effects. Platelet-rich fibrin (PRF) is a great source of growth factors and has been widely used in clinical practice, but few studies explored its application in diabetic wounds. This study was designed to investigate therapeutic effect of PRF as a delivery scaffold of ASCs on promoting healing of diabetic wound in a mouse model. ASCs isolated from subcutaneous fat were cultured in the three-dimensional PRF scaffold for 3 and 7 days, respectively. H&E staining, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM) observation revealed that ASCs could survive and proliferate in PRF. Cell numbers in PRF increased dramatically in the duration of 7 days post-seeding. Meanwhile, it is revealed that conditioned medium of PRF enhanced ASCs proliferation and migration in an in vitro wound model. Furthermore, transplantation of PRF alone or PRF loaded with ASCs improved significantly diabetic wound repair, respectively. Capillary density in wounds received either PRF or PRF-ASCs was significantly higher than wounds without intervention. A in vivo survival assay was also conducted to find that PRF could maintain ASCs cells survive in diabetic wounds. Our study indicated that PRF, in particular that loaded with ASCs, can be considered as a promising approach in the treatment of diabetic wounds.

scholarly journals AURKA Enhances Autophagy of Adipose Derived Stem Cells to Promote Diabetic Wound Repair via Targeting FOXO3a

2020 ◽  
Vol 140 (8) ◽  
pp. 1639-1649.e4
Author(s):  
Yating Yin ◽  
Feifei Chen ◽  
Jianhua Li ◽  
Jing Yang ◽  
Qiang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Repair ◽  
Adipose Derived Stem Cells ◽  
Diabetic Wound

Exosomes from Human Urine-Derived Stem Cells Promote Neurogenesis Via Histone Deacetylase6 Regulation in Ischemic Stroke

2018 ◽  
Author(s):  
Xiaozheng Ling ◽  
Guowei Zhang ◽  
Qingwei Zhu ◽  
Juntao Zhang ◽  
Qing Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ischemic Stroke ◽  
Human Urine

scholarly journals mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1043 ◽  
Author(s):  
Phil Jun Kang ◽  
Daryeon Son ◽  
Tae Hee Ko ◽  
Wonjun Hong ◽  
Wonjin Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Urine ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Patient Specific ◽  
Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

scholarly journals Identification of New Transcription Factors that Can Promote Pluripotent Reprogramming

2021 ◽  
Author(s):  
Ping Huang ◽  
Jieying Zhu ◽  
Yu Liu ◽  
Guihuan Liu ◽  
Ran Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Rna Sequencing ◽  
Human Urine ◽  
Embryonic Stem ◽  
Rna Seq ◽  
Reprogramming Efficiency ◽  
Yamanaka Factors ◽  
Urine Cells

Abstract Background Four transcription factors, Oct4, Sox2, Klf4, and c-Myc (the Yamanka factors), can reprogram somatic cells to induced pluripotent stem cells (iPSCs). Many studies have provided a number of alternative combinations to the non-Yamanaka factors. However, it is clear that many additional transcription factors that can generate iPSCs remain to be discovered. Methods The chromatin accessibility and transcriptional level of human embryonic stem cells and human urine cells were compared by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to identify potential reprogramming factors. Selected transcription factors were employed to reprogram urine cells, and the reprogramming efficiency was measured. Urine-derived iPSCs were detected for pluripotency by Immunofluorescence, quantitative polymerase chain reaction, RNA sequencing and teratoma formation test. Finally, we assessed the differentiation potential of the new iPSCs to cardiomyocytes in vitro. Results ATAC-seq and RNA-seq datasets predicted TEAD2, TEAD4 and ZIC3 as potential factors involved in urine cell reprogramming. Transfection of TEAD2, TEAD4 and ZIC3 (in the presence of Yamanaka factors) significantly improved the reprogramming efficiency of urine cells. We confirmed that the newly generated iPSCs possessed pluripotency characteristics similar to normal H1 embryonic stem cells. We also confirmed that the new iPSCs could differentiate to functional cardiomyocytes. Conclusions In conclusion, TEAD2, TEAD4 and ZIC3 can increase the efficiency of reprogramming human urine cells into iPSCs, and provides a new stem cell sources for the clinical application and modeling of cardiovascular disease. Graphical abstract

scholarly journals Co-Transplantation of Skin-Derived Precursors and Collagen Sponge Facilitates Diabetic Wound Healing by Promoting Local Vascular Regeneration

2015 ◽  
Vol 37 (5) ◽  
pp. 1725-1737 ◽  
Author(s):  
Tingyu Ke ◽  
Mei Yang ◽  
Duo Mao ◽  
Meifeng Zhu ◽  
Yongzhe Che ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Expression Patterns ◽  
Collagen Sponge ◽  
Health Concern ◽  
Diabetic Wound ◽  
Paracrine Signalling ◽  
Vascular Regeneration ◽  
Diabetic Wound Healing

Background/Aims: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery. Methods: SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined. Results and Conclusion: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.

Abstract 262: Derivation of Duchenne Muscular Dystrophy Disease Specific Cardiomyocytes From Patient Urine

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Xuan Guan ◽  
David L Mack ◽  
Claudia M Moreno ◽  
Fernando Santana ◽  
Charles E Murry ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Urine ◽  
Large Scale ◽  
Lentiviral Vector ◽  
Cellular Reprogramming ◽  
Urine Samples ◽  
Pcr Analysis ◽  
Scale Production ◽  
Mechanism Study

Introduction: Human somatic cells can be reprogrammed into primitive stem cells, termed induced pluripotent stem cells (iPSCs). These iPSCs can be extensively expanded in vitro and differentiated into multiple functional cell types, enabling faithful preservation of individual’s genotype and large scale production of disease targeted cellular components. These unique cellular reagents thus hold tremendous potential in disease mechanism study, drugs screening and cell replacement therapy. Due to the genetic mutation of the protein dystrophin, many DMD patients develop fatal cardiomyopathy with no effective treatment. The underlying pathogenesis has not been fully elucidated. Hypothesis: We tested the hypothesis that iPSCs could be generated from DMD patients’ urine samples and differentiated into cardiomyocytes, recapitulating the dystrophic phenotype. Methods: iPSCs generation was achieved by introducing a lentiviral vector expressing Oct4, Sox2, c-Myc and Klf4 into cells derived from patient’s (n=1) and healthy volunteers’ (n=3) urine. Cardiomyocytes were derived by sequentially treating iPSCs with GSK3 inhibitor CHIR99021 and Wnt inhibitor IWP4. Differentiated cardiomyocytes were subjected to calcium imaging, electrophysiology recording, Polymerase Chain Reaction (PCR) analysis, and immunostaining. Results: iPSCs were efficiently generated from human urine samples and further forced to differentiate into contracting cardiomyocytes. PCR analysis and immunostaining confirmed the expression of a panel of cardiac markers. Both normal and patient iPSC derived cardiomyocytes exhibited spontaneous and field stimulated calcium transients (up to 2Hz), as well as action potentials with ventricular-like and nodal-like characteristics. Anti-dystrophin antibodies stained normal iPSC-derived cardiomyocyte membranes but did not react against DMD iPSC-derived cardiomyocytes. Conclusions: Cardiomyocytes can be efficiently generated from human urine, through the cellular reprogramming technology. DMD cardiomyocytes retained the patient’s genetic information and manifested a dystrophin-null phenotype. Functional assessments are underway to determine differences that may exist between genotypes.

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