scholarly journals Vascularization of LBL structured nanofibrous matrices with endothelial cells for tissue regeneration

RSC Advances ◽  
2017 ◽  
Vol 7 (19) ◽  
pp. 11462-11477 ◽  
Author(s):  
Lei Cui ◽  
Jing Li ◽  
Yunze Long ◽  
Min Hu ◽  
Jinqing Li ◽  
...  

The aligned LBL scaffold promoted host vessel infiltration into the scaffolds and integration with in vitro prefabricated vascular structures.

2020 ◽  
Author(s):  
Yao Liu ◽  
Xueying Zhuang ◽  
Si Yu ◽  
Ning Yang ◽  
Jianhong Zeng ◽  
...  

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue.Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42.Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo, and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs.Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.


Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1614
Author(s):  
Paulina Podkalicka ◽  
Jacek Stępniewski ◽  
Olga Mucha ◽  
Neli Kachamakova-Trojanowska ◽  
Józef Dulak ◽  
...  

Inadequate supply of oxygen (O2) is a hallmark of many diseases, in particular those related to the cardiovascular system. On the other hand, tissue hypoxia is an important factor regulating (normal) embryogenesis and differentiation of stem cells at the early stages of embryonic development. In culture, hypoxic conditions may facilitate the derivation of embryonic stem cells (ESCs) and the generation of induced pluripotent stem cells (iPSCs), which may serve as a valuable tool for disease modeling. Endothelial cells (ECs), multifunctional components of vascular structures, may be obtained from iPSCs and subsequently used in various (hypoxia-related) disease models to investigate vascular dysfunctions. Although iPSC-ECs demonstrated functionality in vitro and in vivo, ongoing studies are conducted to increase the efficiency of differentiation and to establish the most productive protocols for the application of patient-derived cells in clinics. In this review, we highlight recent discoveries on the role of hypoxia in the derivation of ESCs and the generation of iPSCs. We also summarize the existing protocols of hypoxia-driven differentiation of iPSCs toward ECs and discuss their possible applications in disease modeling and treatment of hypoxia-related disorders.


Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 877-885 ◽  
Author(s):  
Karsten Grote ◽  
Gustavo Salguero ◽  
Matthias Ballmaier ◽  
Marc Dangers ◽  
Helmut Drexler ◽  
...  

Abstract Tissue regeneration involves the formation of new blood vessels regulated by angiogenic factors. We reported recently that the expression of the angiogenic factor CCN1 is up-regulated under various pathophysiologic conditions within the cardiovascular system. Because CD34+ progenitor cells participate in cardiovascular tissue regeneration, we investigated whether CCN1—detected for the first time in human plasma—promotes the recruitment of CD34+ progenitor cells to endothelial cells, thereby enhancing endothelial proliferation and neovascularization. In this study, we demonstrated that CCN1 and supernatants from CCN1-stimulated human CD34+ progenitor cells promoted proliferation of endothelial cells and angiogenesis in vitro and in vivo. In addition, CCN1 induced migration and transendothelial migration of CD34+ cells and the release of multiple growth factors, chemokines, and matrix metalloproteinase-9 (MMP-9) from these cells. Moreover, the CCN1-specific integrins αMβ2 and αVβ3 are expressed on CD34+ cells and CCN1 stimulated integrin-dependent signaling. Furthermore, integrin antagonists (RGD-peptides) suppressed both binding of CCN1 to CD34+ cells and CCN1-induced adhesion of CD34+ cells to endothelial cells. These data suggest that CCN1 promotes integrin-dependent recruitment of CD34+ progenitor cells to endothelial cells, which may contribute to paracrine effects on angiogenesis and tissue regeneration.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Liling Ren ◽  
Dongyang Ma ◽  
Bin Liu ◽  
Jinda Li ◽  
Jia Chen ◽  
...  

Engineering three-dimensional (3D) vascularized constructs remains a challenge due to the inability to form rich microvessel networks. In this study we engineered a prevascularized 3D cell sheet construct for tissue regeneration using human bone marrow-derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells as cell sources. hMSCs were cultured to form a thick cell sheet, and human umbilical vein endothelial cells (HUVECs) were then seeded on the hMSCs sheet to form networks. The single prevascularized HUVEC/hMSC cell sheet was folded to form a 3D construct by a modified cell sheet engineering technique.In vitroresults indicated that the hMSCs cell sheet promoted the HUVECs cell migration to form networks in horizontal and vertical directions.In vivoresults showed that many blood vessels grew into the 3D HUVEC/hMSC cell sheet constructs after implanted in the subcutaneous pocket of immunodeficient mice. The density of blood vessels in the prevascularized constructs was higher than that in the nonprevascularized constructs. Immunohistochemistry staining further showed thatin vitropreformed human capillaries in the prevascularized constructs anastomosed with the host vasculature to form functional blood vessels. These results suggest the promising potential of this 3D prevascularized construct using hMSCs cell sheet as a platform for wide applications in engineering vascularized tissues.


Author(s):  
Vincenzo Mattei ◽  
Stefano Martellucci ◽  
Fanny Pulcini ◽  
Francesca Santilli ◽  
Maurizio Sorice ◽  
...  

AbstractA new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration. Graphical abstract


2020 ◽  
Author(s):  
Yao Liu ◽  
Xueying Zhuang ◽  
Si Yu ◽  
Ning Yang ◽  
Jianhong Zeng ◽  
...  

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue. Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42. Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo , and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro . Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs. Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.


Author(s):  
D.J.P. Ferguson ◽  
M. Virji ◽  
H. Kayhty ◽  
E.R. Moxon

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.


2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.


1993 ◽  
Vol 70 (04) ◽  
pp. 707-711 ◽  
Author(s):  
Andrew D Blann ◽  
Charles N McCollum

SummaryThe effect of smoking on the blood vessel intima was examined by comparing indices of endothelial activity in serum from smokers with that from non-smokers. Serum from smokers contained higher levels of von Willebrand factor (p <0.01), the smoking markers cotinine (p <0.02) and thiocyanate (p <0.01), and was more cytotoxic to endothelial cells in vitro (p <0.02) than serum from non-smokers. The acute effects of smoking two unfiltered medium tar cigarettes was to briefly increase von Willebrand factor (p <0.001) and cytotoxicity of serum to endothelial cells in vitro (p <0.005), but lipid peroxides or thiocyanate were not increased by this short exposure to tobacco smoke. Although there were correlations between von Willebrand factor and smokers consumption of cigarettes (r = 0.28, p <0.02), number of years smoking (r = 0.41, p <0.001) and cotinine (r = 0.45, p <0.01), the tissue culture of endothelial cells with physiological levels of thiocyanate or nicotine suggested that these two smoking markers were not cytotoxic. They are therefore unlikely to be directly responsible for increased von Willebrand factor in the serum of smokers. We suggest that smoking exerts a deleterious influence on the endothelium and that the mechanism is complex.


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