scholarly journals Adipose-Derived Stem Cells Promote Intussusceptive Lymphangiogenesis by Restricting Dermal Fibrosis in Irradiated Tissue of Mice

2020 ◽  
Vol 21 (11) ◽  
pp. 3885
Author(s):  
Ryohei Ogino ◽  
Kenji Hayashida ◽  
Sho Yamakawa ◽  
Eishin Morita

Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 × 105 ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.

2020 ◽  
Vol 230 (1) ◽  
Author(s):  
Xin Fan ◽  
Kai Li ◽  
Luochen Zhu ◽  
Xin Deng ◽  
Ziqian Feng ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-26
Author(s):  
Jiaxin Zhang ◽  
Yuzhe Liu ◽  
Yutong Chen ◽  
Lei Yuan ◽  
He Liu ◽  
...  

Adipose-derived stem cells (ADSCs) can maintain self-renewal and enhanced multidifferentiation potential through the release of a variety of paracrine factors and extracellular vesicles, allowing them to repair damaged organs and tissues. Consequently, considerable attention has increasingly been paid to their application in tissue engineering and organ regeneration. Here, we provide a comprehensive overview of the current status of ADSC preparation, including harvesting, isolation, and identification. The advances in preclinical and clinical evidence-based ADSC therapy for bone, cartilage, myocardium, liver, and nervous system regeneration as well as skin wound healing are also summarized. Notably, the perspectives, potential challenges, and future directions for ADSC-related researches are discussed. We hope that this review can provide comprehensive and standardized guidelines for the safe and effective application of ADSCs to achieve predictable and desired therapeutic effects.


2020 ◽  
Author(s):  
Xiang Wan ◽  
Min-kai Xie ◽  
Huan Xu ◽  
Zi-wei Wei ◽  
Hai-jun Yao ◽  
...  

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.


2013 ◽  
Vol 13 (2-3) ◽  
pp. 99-102 ◽  
Author(s):  
Keun-A. Chang ◽  
Hee Jin Kim ◽  
Yuyoung Joo ◽  
Sungji Ha ◽  
Yoo-Hun Suh

2018 ◽  
Vol 27 (9) ◽  
pp. 1390-1400 ◽  
Author(s):  
Reiko Iwazawa ◽  
Sayako Kozakai ◽  
Tsukasa Kitahashi ◽  
Kentaro Nakamura ◽  
Ken-ichiro Hata

Cell therapies using adipose-derived stem cells (ADSCs) have been used to treat inflammatory bowel disease (IBD) in human and dog. We previously reported the CellSaic technique, which uses a recombinant scaffold to enhance the efficacy of cell therapy. To examine whether this technique can be applied to cell therapy for colitis, we evaluated the efficacy of CellSaic in colitis mouse models. Colitis mouse models were developed by administering dextran sulfate sodium (DSS) to C57BL/6 mice for 7 days. Then CellSaic comprising human/canine ADSCs (1.2 × 106 cells) or human/canine ADSCs only (1.2 × 106 cells) were administered to the mice. The body weights were measured, and the colon length measurements and histological evaluations were conducted at 7 days after administration. After in vitro culture of human ADSC (hADSC) CellSaic and hADSC spheroids in medium containing TNFα, the levels of the anti-inflammatory protein TSG-6 in each supernatant were measured. Furthermore, we conducted tumorigenicity and general toxicity tests of canine ADSC (cADSC) CellSaic in NOG mice for 8 weeks. In the colitis mouse models, the ADSC CellSaic group presented recovery of body weight and colon length compared with the ADSC-only group. Histological analysis showed that ADSC CellSaic decreased the number of inflammatory cells and repaired ulceration. In vitro, hADSC CellSaic secreted 3.1-fold more TSG-6 than the hADSCs. In addition, tumorigenicity and general toxicity of cADSC CellSaic were not observed. This study suggests that human and canine ADSC CellSaic has a therapeutic effect of colitis in human and dogs.


2019 ◽  
Vol 9 (4) ◽  
pp. 662-667 ◽  
Author(s):  
Faraz Sigaroodi ◽  
Hajar Shafaei ◽  
Mohammad Karimipour ◽  
Mohammad Amin Dolatkhah ◽  
Abbas Delazar

Purpose: Natural biomaterials are a key base in tissue engineering, and collagen, as the maincontent of the extracellular matrix (ECM), is frequently used in tissue engineering. Aloe verahas some therapeutic effects on ulcers, therefore, the use of this natural resource has alwaysbeen considered for improving collagen function. We aimed to evaluate the effect of Aloe vera/Collagen blended on cell viability, cell attachment, and angiogenic potential by determining ofintegrin α1β1 and platelet endothelial cell adhesion molecule (PECAM-1) genes expression inhuman adipose-derived stem cells (hASCs).Methods: In this study, hASCs after harvesting of adipose tissues from abdominal subcutaneousadipose tissue and isolation, were cultured in four groups of control, collagen gel, Aloe veragel, and Aloe vera/collagen blended in vitro environment at 24h and then cell viability wasassessed by MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium) assay. Integrin α1β1 andPECAM-1 genes expression were evaluated by real-time RT-PCR.Results: The results of MTT showed that the combination of Aloe vera/collagen was retained thecell viability at the normal range and improved it. In real-time RT-PCR results, integrin α1β1 andPECAM-1 gene expression were increased in the Aloe vera/collagen blended group comparedto the control group.Conclusion: For tissue engineering purposes, Aloe vera improves collagen properties in theculture of hASCs by increasing the expression of the integrin α1β1 and PECAM-1 genes.<br />


2020 ◽  
Author(s):  
Chaoyu Zhang ◽  
Ting Wang ◽  
Li Zhang ◽  
Penghong Chen ◽  
Shijie Tang ◽  
...  

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.


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