Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering

Kang, Kai; Chuai, Jun-Bo; Xie, Bingteng; Li, Jianzhong; Qü, Hui; Wu, Hua; Fang, Shaohong; Cui, Jinjin; Xiu, Lili; Han, Jincheng; Cao, Tianhui; Leng, Xiaoping; Tian, Hao; Li, Ren‐Ke; Jiang, Shulin

doi:10.1016/j.biomaterials.2019.119574

Cited by 17 publications

(13 citation statements)

References 71 publications

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“…ADSCs have been reported to reside in a lower (i.e., 1–5% O 2 ) oxygen tension than that typically used in ambient cell culture (20–21%) [ 5 ]. Due to the lack of vascularization, in the early period of tissue regeneration, the oxygen tension may be lower than 4% [ 31 ]. Therefore, we used 1% O 2 oxygen tension to simulate the oxygen conditions after cell-scaffold transplantation.…”

Section: Discussionmentioning

confidence: 99%

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

Wan

Xie

et al. 2020

Stem Cell Res Ther

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wan

Xie

et al. 2020

Stem Cell Res Ther

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“…It has also been reported that VEGFA can increase glycolysis and ensure physiological metabolism [20,36]. There is consensus that VEGFR-2 is the main receptor of VEGFA that plays an angiogenic role via tyrosine phosphorylation [31]. Therefore, we believe that in the interaction between ADSCs and HUVECs, VEGFA and VEGFR2 may represent two targeted molecules.…”

Section: Discussionmentioning

confidence: 87%

“…ADSCs have been reported to reside in a lower (i.e., 1-5% O 2 ) oxygen tension than that typically used in ambient cell culture (20-21%) [5]. Due to the lack of vascularization, in the early period of tissue regeneration, the oxygen tension may be lower than 4% [31]. Therefore, we used 1% O2 oxygen tension to simulate the oxygen conditions after cell-scaffold transplantation.…”

Section: Discussionmentioning

confidence: 99%

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

Xiang¹,

Xie²,

Xu³

et al. 2020

Preprint

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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.

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“…It is well known that BMSCs are characterized by multidirectional differentiation and low immunity, and the potential immune-regulating effect of BMScs has garnered increasing attention. BMScs are functional and pivotal cells that repair damaged tissues and organs, including bone tissue, cartilage and joint injury (39). However, the differentiation of BMScs into osteoblasts, lipoblasts or chondroblasts can be inhibited by inflammation, thus affecting the tissue repair process (40).…”

Section: Discussionmentioning

confidence: 99%

Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action

Jiang

Wang

et al. 2020

Mol Med Rep

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The occurrence and development of hyperglycemia-induced inflammation is associated with increased expression of receptor for advanced glycation end products (RAGE) and inflammatory factors, including IL-1β, TnF-α and il-6. Previous studies have reported that the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome interacts with thioredoxin-interacting protein (TXNIP) and serves a crucial role in inflammation. FPS-ZM1 has been identified as target inhibitor of RAGE and has been shown to exert an anti-inflammatory effect in vitro. However, the underlying mechanism by which FPS-ZM1 impacts high glucose (HG)-induced inflammation in bone marrow mesenchymal stem cells (BMScs) remains unclear. The present study explored the regulatory effect of FPS-ZM1 on HG-induced inflammation in BMSCs. Furthermore, the role of the TXNIP/NLRP3 inflammasome signaling pathway in the regulatory effects of FPS-ZM1 on HG-induced inflammation was studied. cell viability was determined using cell counting Kit-8 and western blotting was used to assess the protein expression levels of raGe. eliSa was used to determine the levels of inflammatory markers. Reverse transcription-quantitative Pcr and western blotting were used to measure the mrna and protein expression levels of TXniP, caspase-1, thioredoxin (TRX), NLRP3 and apoptosis-related speck-like protein containing card (aSc). The results revealed that in BMScs, raGe expression was stimulated by HG, an effect which was reversed by treatment with FPS-ZM1. in addition, HG activated inflammatory factors, such as TnF-α, IL-1β and il-6; however, their levels were suppressed when cells were treated with FPS-ZM1 or the TXNIP/NLRP3 pathway inhibitor, resveratrol (Res). Furthermore, FPS-ZM1 inhibited the mrna and protein expression levels of TXniP, caspase-1, NLRP3 and ASC, and promoted TRX expression, which was consistent with the effects of res. These findings indicated that FPS-ZM1 may attenuate HG-induced inflammation in BMSCs. Furthermore, the TXNIP/NLRP3 inflammasome signaling pathway mediated the molecular mechanism underlying this effect.

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Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering

Cited by 17 publications

References 71 publications

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

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

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

Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action

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