Cell-assembled extracellular matrix (CAM): a human biopaper for the biofabrication of pre-vascularized tissues able to connect to the host circulation in vivo

2021 ◽  
Vol 14 (1) ◽  
pp. 015005
Author(s):  
H Oliveira ◽  
C Médina ◽  
G Labrunie ◽  
N Dusserre ◽  
S Catros ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular System ◽  
Circulatory System ◽  
Mice Model ◽  
Tissue Integration ◽  
Tissue Equivalent ◽  
Human Material ◽  
First Time

Abstract When considering regenerative approaches, the efficient creation of a functional vasculature, that can support the metabolic needs of bioengineered tissues, is essential for their survival after implantation. However, it is widely recognized that the post-implantation microenvironment of the engineered tissues is often hypoxic due to insufficient vascularization, resulting in ischemia injury and necrosis. This is one of the main limitations of current tissue engineering applications aiming at replacing significant tissue volumes. Here, we have explored the use of a new biomaterial, the cell-assembled extracellular matrix (CAM), as a biopaper to biofabricate a vascular system. CAM sheets are a unique, fully biological and fully human material that has already shown stable long-term implantation in humans. We demonstrated, for the first time, the use of this unprocessed human ECM as a microperforated biopaper. Using microvalve dispensing bioprinting, concentrated human endothelial cells (30 millions ml−1) were deposited in a controlled geometry in CAM sheets and cocultured with HSFs. Following multilayer assembly, thick ECM-based constructs fused and supported the survival and maturation of capillary-like structures for up to 26 d of culture. Following 3 weeks of subcutaneous implantation in a mice model, constructs showed limited degradative response and the pre-formed vasculature successfully connected with the host circulatory system to establish active perfusion.This mechanically resilient tissue equivalent has great potential for the creation of more complex implantable tissues, where rapid anastomosis is sine qua non for cell survival and efficient tissue integration.

scholarly journals Dynamics of intravital concentration of amino acid metabolites in human brain in post-traumatic period

2019 ◽  
Vol 484 (2) ◽  
pp. 238-242
Author(s):  
N. A. Semenova ◽  
P. E. Menshchikov ◽  
A. V. Manzhurtsev ◽  
M. V. Ublinskiy ◽  
T. A. Akhadov ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Amino Acid ◽  
Human Brain ◽  
Leading Role ◽  
Acid Metabolites ◽  
Post Traumatic ◽  
First Time

Intracellular concentrations of N acetyaspartate (NAA), aspartate (Asp) and glutamate (Glu) were determined for the first time in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and late post-traumatic period was investigated. In MRI‑negative frontal lobes one day after injury Asp and Glu levels were found to decrease by 45 and 35%, respectively, while NAA level decreased by only 16%. A negative correlation between NAA concentration and the ratio of Asp/Glu concentrations was found. In the long-term period, Glu level returned to normal, Asp level remained below normal by 60%, NAA level was reduced by 65% relative to normal, and Asp/Glu ratio significantly decreased. The obtained results revealed leading role of the neuronal aspartate-malate shuttle in violation of NAA synthesis.

Computational Study on the Effects of Peripheral Vessel Network on Blood Flow in the Arterial Circle of Willis

2007 ◽  
Author(s):  
Shigefumi Tokuda ◽  
Takeshi Unemura ◽  
Marie Oshima
Keyword(s):  
Numerical Simulation ◽  
Blood Flow ◽  
Boundary Conditions ◽  
Vascular System ◽  
Computational Study ◽  
Circulatory System ◽  
Biological Data ◽  
Patient Specific ◽  
Peripheral Vessel

Cerebrovascular disorder such as subarachnoid hemorrhage (SAH) is 3rd position of the cause of death in Japan [1]. Its initiation and growth are reported to depend on hemodynamic factors, particularly on wall shear stress or blood pressure induced by blood flow. In order to investigate the information on the hemodynamic quantities in the cerebral vascular system, the authors have been developing a computational tool using patient-specific modeling and numerical simulation [2]. In order to achieve an in vivo simulation of living organisms, it is important to apply appropriate physiological conditions such as physical properties, models, and boundary conditions. Generally, the numerical simulation using a patient-specific model is conducted for a localized region near the research target. Although the analysis region is only a part of the circulatory system, the simulation has to include the effects from the entire circulatory system. Many studies have carried out to derive the boundary conditions to model in vivo environment [3–5]. However, it is not easy to obtain the biological data of cerebral arteries due to head capsule.

Extracellular Matrix Protein Matrilin-4 Regulates HSC Stress Response

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 601-601
Author(s):  
Hannah Uckelmann ◽  
Sandra Blaszkiewicz ◽  
Marieke Essers
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Matrix Protein ◽  
Bone Marrow Cells ◽  
Blood System ◽  
Extracellular Matrix Protein

Abstract The life-long maintenance of the blood system is accomplished by a pool of self-renewing multipotent hematopoietic stem cells (HSCs). Adult HSCs are found in a dormant state for most of their lifetime, entering cell cycle only to maintain homeostatic blood supply. Under stress conditions such as infection or chemotherapy, the loss of mature blood cells leads to an activation of dormant HSCs to replenish the blood system. Gene expression analysis performed by our group now revealed that Matrilin-4 is highly expressed in long-term HSCs (LT-HSCs) compared to short-term HSCs or committed progenitors, suggesting a potential role of Matrilin-4 in HSC function. Matrilin-4 is a member of the von Willebrand factor A-containing family of extracellular adapter proteins, which form filamentous structures outside of cells. Using mice lacking the entire family of Matrilins (1-4) we have investigated the role of Matrilins in HSC function. Constitutive Matrilin 1-4 KO mice exhibit normal hematopoiesis with a mild reduction in bone marrow cellularity and LSK numbers. However, when Matrilin KO bone marrow cells are pushed to proliferate in competitive transplantation assays with wildtype (WT) cells, they show a striking growth advantage. In a competitive transplant setting, where bone marrow cells of Matrilin KO versus WT mice are transplanted in a 1:1 ratio, the KO cells outcompete WT cells within four weeks, reaching a 90% chimerism at 16 weeks. This competitive advantage of Matrilin KO cells is evident in the long-term stem cell level as well as progenitors and is consistent in secondary transplants. To explore this remarkable phenotype, we performed single cell transplantation experiments of LT-HSCs and observed a more rapid reconstitution of peripheral blood cell levels of KO HSCs compared to WT controls. Confirming this growth advantage, Matrilin KO LSK cells show higher colony forming and serial replating potential in vitro, which can be rescued by the addition of recombinant or overexpressed Matrilin-4. While Matrilin-4 is highly expressed in homeostatic HSCs, in vivo treatment with IFNα or other inflammatory agents, such as LPS or G-CSF result in a dramatic downregulation (25-fold) of Matrilin-4 on the transcript as well as the protein level. Moreover, Matrilin KO HSCs are more sensitive to inflammatory stress, as they show a 2-fold stronger cell cycle activation in response to IFNα in vivo. Critically, Matrilin-4 KO HSCs return to the G0 state of the cell cycle normally after stress-induced activation and transplantation, thereby preventing their exhaustion. In summary, we show that the extracellular matrix protein Matrilin-4 is a novel component of the HSC niche, regulating HSC stress response. Surprisingly, HSCs lacking this extracellular matrix protein show a higher HSC potential due to an accelerated response to stress. Our data suggest that high expression of Matrilin-4 in LT-HSCs confers a resistance to stress stimuli. In situations of acute stress such as infection or transplantation however, this protection is rapidly lost to allow HSCs to efficiently replenish the blood system. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jin Wook Hwang ◽  
Sungtae Kim ◽  
Se Won Kim ◽  
Jong Ho Lee
Keyword(s):  
Extracellular Matrix ◽  
Bottom Layer ◽  
Cross Linking ◽  
Tissue Integration ◽  
Barrier Membrane ◽  
Synthetic Materials ◽  
Rabbit Tibia ◽  
Porcine Pericardium ◽  
Degradation Time

Absorbable extracellular matrix (ECM) membrane has recently been used as a barrier membrane (BM) in guided tissue regeneration (GTR) and guided bone regeneration (GBR). Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymesin vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP) showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18–0.35 mm) but with excellent mechanical properties. Tensile strength of APP was14.15±2.24 MPa. Inin vivoexperiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months.

scholarly journals Latent Antigen Vaccination in a Model Gammaherpesvirus Infection

2001 ◽  
Vol 75 (17) ◽  
pp. 8283-8288 ◽  
Author(s):  
Edward J. Usherwood ◽  
Kimberley A. Ward ◽  
Marcia A. Blackman ◽  
James P. Stewart ◽  
David L. Woodland
Keyword(s):  
Latent Infection ◽  
Model Systems ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Associated Proteins ◽  
Infected Cells ◽  
The Impact ◽  
First Time

ABSTRACT Vaccines that can reduce the load of latent gammaherpesvirus infections are eagerly sought. One attractive strategy is vaccination against latency-associated proteins, which may increase the efficiency with which T cells recognize and eliminate latently infected cells. However, due to the lack of tractable animal model systems, the effect of latent-antigen vaccination on gammaherpesvirus latency is not known. Here we use the murine gammaherpesvirus model to investigate the impact of vaccination with the latency-associated M2 antigen. As expected, vaccination had no effect on the acute lung infection. However, there was a significant reduction in the load of latently infected cells in the initial stages of the latent infection, when M2 is expressed. These data show for the first time that latent-antigen vaccination can reduce the level of latency in vivo and suggest that vaccination strategies involving other latent antigens may ultimately be successfully used to reduce the long-term latent infection.

scholarly journals Maturation of Nephrons by Implanting hPSC-Derived Kidney Progenitors Under Kidney Capsules of Unilaterally Nephrectomized Mice

2021 ◽  
Author(s):  
Xin Yu ◽  
Shan Jiang ◽  
Kailin Li ◽  
Xianzhen Yang ◽  
Zhihe Xu ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Vascular System ◽  
Human Kidney ◽  
Target Cells ◽  
Mice Model ◽  
Immunodeficient Mice ◽  
Filtration Barrier ◽  
Kidney Organoids

Abstract Background Human pluripotent stem cell (hPSCs)-derived kidney organoids may contribute to disease modeling and generation of kidney replacement tissues. However, realization of such applications requires the induction of hPSCs into functional mature organoids. One of the key questions for this process is whether a specific vascular system exists for nephrogenesis. Our previous study showed that implantation of hPSC-derived organoids below the kidney capsules of unilaterally nephrectomized immunodeficient mice for a short-term (2 weeks) resulted in the enlargement of organoids and production of vascular cells, although signs of maturation were lacking. Methods In this study, organoids are induced in vitro during 15 days and then sub-capsularly grafted into kidneys, we used the same unilaterally nephrectomized immunodeficient mice model to examine whether a medium -term (4 weeks) implantation could improve organoid maturation and vascularization, as evaluated by immunofluorescence and transmission electron microscopy(TEM). Results We demonstrate that after 2–4 weeks implantation, implanted renal organoids can form host-derived vascularization and mature in the absence of any exogenous vascular endothelial growth factor. Glomerular filtration barrier maturation was evidenced by glomerular basement membrane deposition, perforated glomerular endothelial cell development, as well as apical to basal podocyte polarization. A polarized monolayer epithelium and extensive brush border were also observed for tubular epithelial cells. Conclusions Our results indicate that the in vivo microenvironment is important for the maturation of human kidney organoids. Stromal expansion and a reduction of nephron structures were observed following longer-term (12 weeks) implantation,suggesting effects on off-target cells during the induction process. Accordingly, induction efficiency and transplantation models should be improved in the future.

scholarly journals Reproductive biology and embryonal development of pacific capelin Mallotus villosus catervarius from the Tauiskaya Bay (northern part of the Okhotsk Sea)

2016 ◽  
Vol 185 (2) ◽  
pp. 49-66
Author(s):  
Ravil R. Yusupov ◽  
Maria Yu. Santalova
Keyword(s):  
Reproductive Biology ◽  
Vascular System ◽  
Okhotsk Sea ◽  
Mallotus Villosus ◽  
Embryonal Development ◽  
The Pacific ◽  
Capelin Mallotus Villosus ◽  
First Time ◽  
Consequent Increase

Reproductive biology of embryogeny and early ontogenesis is considered for pacific capelin Mallotus villosus catervarius (Pennant) from the Tauiskaya Bay in the northern Okhotsk Sea on the data of long-term sampling. The stages of periblastic sinus and Kupffer’s vesicle are described for the first time for the genus Mallotus. Results of the study allow to assume development of the embryonic vascular system of respiration for the capelin embryo. Tendency to the pacific capelin fecundity increasing is observed in the last five decades conditioned by its abundance lowering and consequent increase of the older fish percentage.

scholarly journals In vivo monitoring of tissue regeneration using a ratiometric lysosomal AIE probe

2020 ◽  
Vol 11 (12) ◽  
pp. 3152-3163 ◽  
Author(s):  
Xiujuan Shi ◽  
Neng Yan ◽  
Guangle Niu ◽  
Simon H. P. Sung ◽  
Zhiyang Liu ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Lysosomal Ph ◽  
In Vivo Monitoring ◽  
Ratiometric Probe ◽  
First Time

An AIE-active ratiometric probe for the first time achieved the long-term quantification of lysosomal pH during the medaka larva's caudal fin regeneration.

scholarly journals Riligustilide Attenuated Renal Injury by the Blockade of Renin

2018 ◽  
Vol 50 (2) ◽  
pp. 654-667 ◽  
Author(s):  
Juan Kong ◽  
Li Han ◽  
Han Su ◽  
Yihan Hu ◽  
Xueshi Huang ◽  
...  
Keyword(s):  
Renal Injury ◽  
Chinese Herb ◽  
Underlying Mechanism ◽  
Vehicle Group ◽  
Mice Model ◽  
Kidney Fibrosis ◽  
Term Administration

Background/Aims: Nephropathy related with renin can be alleviated with ACE-inhibitors or AT1R blockers, whereas they might be ineffective after long-term administration because of a feedback production of enhanced renin. Therefore, it is urgent to develop a new category of anti-nephropathy medicine directly targeting renin. Riligustilide (C20), originally isolated from the Chinese herb Ligusticumporteri, a rhizome, was confirmed effective against many diseases. Methods: The therapeutic effect of C20 on renal injury and its underlying mechanism were investigated in three different nephrotic models, which were spontaneously hypertension rats (SHR) model, diabetic nephropathy in BTBR ob/ob mice model and 5/6-nephrectomized (5/6NX) rats model. Results: The intensity of kidney fibrosis was extensively decreased in the C20-treated rats compared to the vehicle animals. C20 significantly alleviated renal injury much more in 5/6 NX rats than in vehicle group. The rats in 5/6 NX without administrated C20 developed albuminuria earlier with more severe symptoms. Additionally, our findings showed that C20 down-regulated the renin expression and relocation of CREB-CBP complex in vivo and in vitro. Conclusion: C20 plays importantly reno-protective roles most likely through the relocation of CREB-CBP complex.

scholarly journals The horse as a model for translational orthopedic research: examples of studies on the regeneration of cartilage and bone conducted in Costa Rica

2019 ◽  
Vol 37 (3) ◽  
pp. 9-10
Author(s):  
Rafael Vindas Bolaños ◽  
Jos Malda ◽  
René Van Weeren ◽  
Janny De Grauw
Keyword(s):  
Bone Defects ◽  
Chondral Defects ◽  
Fixation Techniques ◽  
Equine Studies ◽  
First Time ◽  
Adhesive Capacity ◽  
Stimulation Of ◽  
Long Term Studies

The paper provides results published or to be published of long-term in vivo equine studies to evaluate techniques of possible regenerative matrices of cartilage and bone, by means of cell-free implants or stimulation of the bone marrow. From the fixation techniques analyzed, it can be concluded that the best alternatives are the pressure technique for subchondral defects and a novel hydrogel with self-adhesive capacity for chondral defects. The equine coxal tuberosity was used for the first time as a model for regeneration studies of bone defects, analyzing scaffolds based on tricalcium phosphate, polymers and nanoparticles, by means of 3-D printing. Osteoconductivity, osteoinductivity, and the importance of microporosity were documented.Given that decellularized materials do not always give significant desired results in the regeneration of cartilage, it is important to conduct long-term studies. The technique of nanofracture and a novel self-adhesive hydrogel in the knee of the equine showed promising preliminary results in the regeneration of cartilage.The knee and the coxal tuberosity of the horse represent models of studying cartilage and bone regeneration in a true translational sense as a source of highly valuable information for clinical studies, for both horses and humans.

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