scholarly journals Adipose-Derived Stem Cells Promote Bone Coupling in Bisphosphonate-Related Osteonecrosis of the Jaw by TGF-β1

2021 ◽  
Vol 9 ◽  
Author(s):  
Xian Dong ◽  
Linhai He ◽  
Xiaolong Zang ◽  
Yang He ◽  
Jingang An ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Conditioned Medium ◽  
Bone Matrix ◽  
Neutralizing Antibody ◽  
Clinical Samples ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Tgf Β1

This study aimed to investigate molecularly targeted therapy to revive bone remodeling and prevent BRONJ by local adipose-derived stem cells (ADSCs) transplantation. Clinical samples of BRONJ and healthy jawbones were used to examine the bone coupling-related cells and TGF-β1 expression. Bone coupling-related cells and TGF-β1 expression were also assessed in BRONJ-like animal model to confirm the results in clinical samples. ADSCs were locally administered in vivo and the therapeutic effects were evaluated by gross observation, radiological imaging, and histological examination. Furthermore, ADSCs-conditioned medium (ADSCs-CM) and neutralizing antibody were applied to assess the effects of ADSCs-derived TGF-β1 on restoring bone coupling in vivo. Osteoclast formation and resorption assays were performed to evaluate the effects of ADSCs-derived TGF-β1 on ZA-treated pre-osteoclasts. Cell migration was performed to assess the effects of ADSCs-derived TGF-β1 on patients’ bone marrow stem cells (BMSCs). The number of osteoclasts, Runx2-positive bone-lining cells (BLCs) and TGF-β1 expression were decreased in BRONJ and animal model jaw bone samples. These reductions were significantly rescued and necrotic jawbone healing was effectively promoted by local ADSCs administration in BRONJ-like animal models. Mechanistically, ADSCs-CM mainly contributed to promoting bone coupling, while TGF-β1 neutralizing antibody in the conditioned medium inhibited these effects. Besides, osteoclastogenesis and patients’ BMSCs migration were also rescued by ADSCs-derived TGF-β1. Furthermore, bone resorption-released bone matrix TGF-β1, together with ADSCs-derived TGF-β1, synergistically contributed to rescuing BMSCs migration. Collectively, ADSCs promoted bone healing of BRONJ by TGF-β1-activated osteoclastogenesis and BMSCs migration capacities.

scholarly journals Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by up-regulation of angiogenesis and glycolysis

2020 ◽  
Author(s):  
Xiang Wan ◽  
Min-kai Xie ◽  
Huan Xu ◽  
Zi-wei Wei ◽  
Hai-jun Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Vein ◽  
Urethral Reconstruction ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Promising Alternative ◽  
Hypoxia Preconditioning ◽  
Novel Scaffold

Abstract Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia preconditioned ADSCs, compared to normxia preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism.Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits.Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology and enhanced angiogenesis (p < 0.05). Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.

scholarly journals Human Adipose-Derived Stem Cells’ Paracrine Factors in Conditioned Medium Can Enhance Porcine Oocyte Maturation and Subsequent Embryo Development

2021 ◽  
Vol 22 (2) ◽  
pp. 579
Author(s):  
Seok Hee Lee
Keyword(s):  
Stem Cells ◽  
Conditioned Medium ◽  
Embryo Development ◽  
Oocyte Maturation ◽  
Oocyte Development ◽  
Adipose Derived Stem Cells ◽  
Paracrine Factors ◽  
Porcine Oocyte

An essential requirement for the success of in vitro maturation (IVM) of the oocyte is to provide an optimal microenvironment similar to in vivo conditions. Recently, somatic cell-based coculture or supplementation of a conditioned medium during IVM has been performed to obtain better quality of oocytes, because they mimic the in vivo reproductive tract by secreting paracrine factors. In this study, human adipose-derived stem cells (ASC) and their conditioned medium (ASC-CM) were applied to IVM of porcine oocytes to evaluate the effectiveness of ASC on oocyte development and subsequent embryo development. In results, both ASC and ASC-CM positively influence on oocyte maturation and embryo development by regulating growth factor receptors (VEGF, FGFR, and IGFR), apoptosis (BCL2), cumulus expansion (PTGS2, HAS2, and TNFAIP6), and oocyte maturation-related genes (GDF9 and BMP15). In particular, the fluorescence intensity of GDF9 and BMP15 was markedly upregulated in the oocytes from the ASC-CM group. Furthermore, significantly high levels of growth factors/cytokine including VEGF, bFGF, IGF-1, IL-10, and EGF were observed in ASC-CM. Additionally, the ASC-CM showed active scavenging activity by reducing the ROS production in a culture medium. Consequently, for the first time, this study demonstrated the effect of human ASC-CM on porcine oocyte development and the alteration of mRNA transcript levels in cumulus–oocyte complexes.

scholarly journals Combination of Lyophilized Adipose-Derived Stem Cells Concentrated Conditioned Medium and Polysaccharide Hydrogel in the Inhibition of Hypertrophic Scarring

2020 ◽  
Author(s):  
Chaoyu Zhang ◽  
Ting Wang ◽  
Li Zhang ◽  
Penghong Chen ◽  
Shijie Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Conditioned Medium ◽  
Hypertrophic Scar ◽  
Dose Group ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Adipose Derived Stem Cells ◽  
Hypertrophic Scarring ◽  
Rabbit Ear ◽  
Polysaccharide Hydrogel

Abstract BackgroundMesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scar. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cells conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. MethodsIn the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cells concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. ResultsWe noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated.ConclusionsAltogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect, and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.

scholarly journals Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by upregulation of angiogenesis and glycolysis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiang Wan ◽  
Min-kai Xie ◽  
Huan Xu ◽  
Zi-wei Wei ◽  
Hai-jun Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Vein ◽  
Urethral Reconstruction ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Promising Alternative ◽  
Hypoxia Preconditioning ◽  
Novel Scaffold

Abstract Rationale Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia-preconditioned ADSCs, compared to normoxia-preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism. Methods In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits. Results The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis, and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology, and enhanced angiogenesis (p < 0.05). Conclusions Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.

scholarly journals Hypoxia-Preconditioned Adipose-Derived Stem Cells Combined with Scaffold Promote Urethral Reconstruction by Up-Regulation of Angiogenesis and Glycolysis

2020 ◽  
Author(s):  
Xiang Wan ◽  
Min-kai Xie ◽  
Huan Xu ◽  
Zi-wei Wei ◽  
Hai-jun Yao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Vein ◽  
Urethral Reconstruction ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Promising Alternative ◽  
Hypoxia Preconditioning ◽  
Novel Scaffold

Abstract Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia preconditioned ADSCs, compared to normxia preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism.Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits.Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology and enhanced angiogenesis (p < 0.05). Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zetao Chen ◽  
Yihong Chen ◽  
Yan Li ◽  
Weidong Lian ◽  
Kehong Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
Critical Role ◽  
Glioma Stem Cells ◽  
Promoter Regions ◽  
Aberrant Expression ◽  
Smad Pathway ◽  
Tgf Β1

AbstractGlioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-β1 gene, upregulated TGF-β1 expression, and ultimately activated the TGF-β/smad pathway. Silencing TGF-β1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-β/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients.

scholarly journals A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Thakoon Thitiset ◽  
Siriporn Damrongsakkul ◽  
Supansa Yodmuang ◽  
Wilairat Leeanansaksiri ◽  
Jirun Apinun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Alp Activity

Abstract Background A novel biodegradable scaffold including gelatin (G), chitooligosaccharide (COS), and demineralized bone matrix (DBM) could play a significant part in bone tissue engineering. The present study aimed to investigate the biological characteristics of composite scaffolds in combination of G, COS, and DBM for in vitro cell culture and in vivo animal bioassays. Methods Three-dimensional scaffolds from the mixture of G, COS, and DBM were fabricated into 3 groups, namely, G, GC, and GCD using a lyophilization technique. The scaffolds were cultured with mesenchymal stem cells (MSCs) for 4 weeks to determine biological responses such as cell attachment and cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, cell morphology, and cell surface elemental composition. For the in vivo bioassay, G, GC, and GCD, acellular scaffolds were implanted subcutaneously in 8-week-old male Wistar rats for 4 weeks and 8 weeks. The explants were assessed for new bone formation using hematoxylin and eosin (H&E) staining and von Kossa staining. Results The MSCs could attach and proliferate on all three groups of scaffolds. Interestingly, the ALP activity of MSCs reached the greatest value on day 7 after cultured on the scaffolds, whereas the calcium assay displayed the highest level of calcium in MSCs on day 28. Furthermore, weight percentages of calcium and phosphorus on the surface of MSCs after cultivation on the GCD scaffolds increased when compared to those on other scaffolds. The scanning electron microscopy images showed that MSCs attached and proliferated on the scaffold surface thoroughly over the cultivation time. Mineral crystal aggregation was evident in GC and greatly in GCD scaffolds. H&E staining illustrated that G, GC, and GCD scaffolds displayed osteoid after 4 weeks of implantation and von Kossa staining confirmed the mineralization at 8 weeks in G, GC, and GCD scaffolds. Conclusion The MSCs cultured in GCD scaffolds revealed greater osteogenic differentiation than those cultured in G and GC scaffolds. Additionally, the G, GC, and GCD scaffolds could promote in vivo ectopic bone formation in rat model. The GCD scaffolds exhibited maximum osteoinductive capability compared with others and may be potentially used for bone regeneration.

scholarly journals Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruijie Zeng ◽  
Jinghua Wang ◽  
Zewei Zhuo ◽  
Yujun Luo ◽  
Weihong Sha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Necrotizing Enterocolitis ◽  
Therapeutic Effects ◽  
Beneficial Effects ◽  
Pediatric Diseases ◽  
Gastrointestinal Conditions ◽  
Different Types ◽  
Novel Therapeutic Strategies

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.

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