Minimal Functional Clusters Predict the Probability of Reentry in Cardiac Fibrotic Tissue

2021 ◽  
Vol 127 (9) ◽  
Author(s):  
Farhad Pashakhanloo ◽  
Alexander V. Panfilov
Keyword(s):  
Fibrotic Tissue

Gene expression analysis of metabolic markers during bone regeneration in a rat model

2014 ◽  
Vol 23 (03) ◽  
pp. 207-211
Author(s):  
C. Kasch ◽  
A. Osterberg ◽  
Thordis Granitzka ◽  
T. Lindner ◽  
M. Haenle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Saline Solution ◽  
Female Rats ◽  
Synthesis Rate ◽  
Metabolic Markers ◽  
Expression Levels ◽  
Fibrotic Tissue ◽  
Intermittent Pth ◽  
Lower Expression

SummaryThe RANK/RANKL/OPG system plays an important role in the regulation of bone metabolism and bony integration around implants. The aim of this study was to analyse gene expression of OPG, RANK, and RANKL in regenerating bone during implant integration. Additionally, the effect of intermittent para - thyroid hormone (PTH) treatment was analysed. A titanium chamber was implanted in the proximal tibiae of 48 female rats. The animals received either human PTH or saline solution (NaCl). After 21 and 42 days, RNA was isolated from tissue adjacent to the implant and expression of RANK, RANKL, and OPG was analysed. After 21 days, very low expression levels of all genes were shown. In contrast, increased gene expression after 42 days was determined. Expression of RANK and RANKL was lower than that for OPG. The lower expression levels after 21 days might be due to still ossifying, fibrotic tissue around the titanium chamber. An increased OPG synthesis rate associated with decreased RANKL expression after 42 days revealed bone-forming processes. Despite significant differences in gene expression between the time points, only slight differences were observed between application of intermittent PTH and NaCl after a period of 42 days.

scholarly journals Direct contribution of skeletal muscle mesenchymal progenitors to bone repair

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anais Julien ◽  
Anuya Kanagalingam ◽  
Ester Martínez-Sarrà ◽  
Jérome Megret ◽  
Marine Luka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Healing ◽  
Bone Repair ◽  
Fibrotic Response ◽  
Mesenchymal Progenitors ◽  
Fibrotic Tissue ◽  
Bone Injury ◽  
Single Cell Rna Sequencing ◽  
Musculoskeletal Trauma

AbstractBone regenerates by activation of tissue resident stem/progenitor cells, formation of a fibrous callus followed by deposition of cartilage and bone matrices. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to bone mediate the initial fibrotic response to bone injury and also participate in cartilage and bone formation. Combined lineage and single-cell RNA sequencing analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in chondrogenesis after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors exhibit altered fibrogenesis and chondrogenesis. This leads to impaired bone healing, which is due to accumulation of fibrotic tissue originating from skeletal muscle and can be corrected by the anti-fibrotic agent Imatinib. These results elucidate the central role of skeletal muscle in bone regeneration and provide evidence that skeletal muscle can be targeted to prevent persistent callus fibrosis and improve bone healing after musculoskeletal trauma.

scholarly journals Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis

2011 ◽  
Vol 301 (6) ◽  
pp. G945-G949 ◽  
Author(s):  
Carol A. de la Motte
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Intestinal Inflammation ◽  
Cellular Mechanisms ◽  
Matrix Component ◽  
Matrix Deposition ◽  
Fibrotic Tissue ◽  
Myofibroblast Phenotype ◽  
Extracellular Matrix Deposition ◽  
Chronic Intestinal Inflammation

The causes of fibrosis, or the inappropriate wound healing, that follows chronic intestinal inflammation are not well defined and likely involve the contributions of multiple cellular mechanisms. As other articles in this series confirm, inflammatory cytokines clearly play a role in driving cell differentiation to the myofibroblast phenotype, promoting proliferation and extracellular matrix deposition that are characteristic of fibrotic tissue. However, controlling the balance of cytokines produced and process of myofibroblast differentiation appears to be more complex. This review considers ways in which hyaluronan, an extracellular matrix component that is remodeled during the progression of colitis, may provide indirect as well as direct cues that influence the balancing act of intestinal wound healing.

scholarly journals Influence of Fibrotic Tissue Arrangement on Intracardiac Electrograms During Persistent Atrial Fibrillation

2019 ◽  
Author(s):  
Jorge Sánchez ◽  
Mark Nothstein ◽  
Laura Unger ◽  
Javier Saiz ◽  
Beatriz Trénor Gomis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Persistent Atrial Fibrillation ◽  
Fibrotic Tissue

scholarly journals CD47 prevents the elimination of diseased fibroblasts in scleroderma

2020 ◽  
Author(s):  
Tristan Lerbs ◽  
Lu Cui ◽  
Megan E. King ◽  
Tim Chai ◽  
Claire Muscat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Autoimmune Disease ◽  
Skin Fibrosis ◽  
Transfer Model ◽  
Self Renewal ◽  
Syngeneic Mouse ◽  
Fibrotic Tissue

AbstractScleroderma is a devastating fibrotic autoimmune disease. Current treatments are partly effective in preventing disease progression, but do not remove fibrotic tissue. Here, we evaluated whether scleroderma fibroblasts take advantage of the “don’t-eat-me-signal” CD47 and whether blocking CD47 enables the body’s immune system to get rid of diseased fibroblasts. To test this approach, we used a Jun-inducible scleroderma model. We first demonstrated in patient samples that scleroderma upregulated JUN and increased promotor accessibilities of both JUN and the CD47. Next, we established our scleroderma model demonstrating that Jun mediated skin fibrosis through the hedgehog-dependent expansion of CD26+Sca1-fibroblasts in mice. In a niche-independent adaptive transfer model, JUN steered graft survival and conferred increased self-renewal to fibroblasts. In vivo, JUN enhanced the expression of CD47, and inhibiting CD47 eliminated an ectopic fibroblast graft and increased in vitro phagocytosis. In the syngeneic mouse, depleting macrophages ameliorated skin fibrosis. Therapeutically, combined CD47 and IL6 blockade reversed skin fibrosis in mice and led to the rapid elimination of ectopically transplanted scleroderma cells. Altogether, our study is the first to demonstrate the efficiency of combining different immunotherapies in treating scleroderma and provide a rationale for combining CD47 and IL6 inhibition in clinical trials.

Improved Survival of Macroencapsulated Islets of Langerhans by Preimplantation of the Immunoisolating Device: A Morphometric Study

2003 ◽  
Vol 12 (4) ◽  
pp. 407-412 ◽  
Author(s):  
E. Rafael ◽  
G. S. Wu ◽  
K. Hultenby ◽  
A. Tibell ◽  
A. Wernerson
Keyword(s):  
Neurological Disorders ◽  
Endocrine Cells ◽  
Morphometric Study ◽  
Islet Graft ◽  
Β Cells ◽  
Physiological Conditions ◽  
Fibrotic Tissue ◽  
Device Implantation ◽  
Sd Rat ◽  
Sd Rats

Encapsulation of cells in a semipermeable membrane may in the future provide an opportunity to treat a variety of endocrine and neurological disorders, without the need for lifelong immunosuppression. The physiological conditions in the device are crucial factors for graft survival. Previously, we have shown that the exchange across the immunoisolating membrane and the microcirculation around the TheraCyte™ device increase around 3 months after implantation. The aim of this study was to determine whether preimplantation of the TheraCyte™ device would improve the survival of a later transplanted islet graft. A TheraCyte™ device was implanted SC on one side of the back of a nondiabetic SD rat. After 3 months, 1500 islets isolated from SD rats were transplanted via the device port. At the same time, another device, loaded with the same number of islets, was implanted on the other side of the back. Both devices were explanted 2 weeks after islet transplantation (i.e., 3.5 months and 0.5 month after device implantation, respectively). Six pairs of devices were evaluated by morphometery. The volume densities of viable islets were 0.22 ± 0.04 in the preimplanted device vs. 0.06 ± 0.03 in the nonpreimplanted one (p < 0.05). The corresponding volume densities of fibrosis and necrosis were 0.64 ± 0.13 vs. 0.85 ± 0.08 (p < 0.05) and 0.11 ± 0.14 vs. 0.09 ± 0.07 (ns), respectively. When the absolute volumes (mm3) were calculated, preimplanted devices contained 1.1 ± 0.7 endocrine cells while nonpreimplanted ones contained 0.4 ± 0.2 (p < 0.05). The percentages of insulin-positive β-cells in the preimplanted versus nonpreimplanted device were 80 ± 5% and 67 ± 6%, respectively (p < 0.01). The corresponding volumes of fibrotic tissue were 3.0 ±1.8 vs. 5.2 ± 1.2 (p < 0.05), while the amount of necrotic tissue did not differ significantly (0.42 ± 0.5 vs. 0.50 ± 0.3). Preimplantation of the TheraCyte™ device seems to improve the survival of an encapsulated islet graft and reduce fibroblast outgrowth in the device.

Asymptomatic fibrous dysplasia of the temporal bone

2015 ◽  
Vol 129 (S2) ◽  
pp. S42-S45 ◽  
Author(s):  
T Kimitsuki ◽  
S Komune
Keyword(s):  
Computed Tomography ◽  
Fibrous Dysplasia ◽  
Temporal Bone ◽  
Watchful Waiting ◽  
Unknown Origin ◽  
Fibrotic Tissue ◽  
Slow Progression ◽  
Bone Trabeculae ◽  
The Right ◽  
Tomography Scan

AbstractIntroduction:Fibrous dysplasia is a bone disorder of unknown origin in which normal bone is replaced with fibrotic tissue and disorganised bone trabeculae. The temporal bone is rarely affected. Because of the slowly progressive course of the disease, many mild cases may never be recognised and are found incidentally. We present a patient with fibrous dysplasia of the right temporal bone, who had few complaints.Objective:A 62-year-old man was incidentally found to have fibrous dysplasia of the temporal bone on routine computed tomography scan.Method:One case report.Results:Computed tomography showed a thickening of the right temporal bone with a ground-glass appearance. The 62-year-old man opted for watchful waiting.Conclusion:We have presented an asymptomatic fibrous dysplasia of the temporal bone. Mild cases may never be recognised and are found incidentally because of their slow progression.

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