scholarly journals Recombinant COL6 α2 as a Self-Organization Factor That Triggers Orderly Nerve Regeneration Without Guidance Cues

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhou Fang ◽  
Jian-Long Zou
Keyword(s):  
Nerve Regeneration ◽  
Ex Vivo ◽  
Self Organization ◽  
Collagen Vi ◽  
Defect Model ◽  
Ordering Effects ◽  
Large Molecular Weight ◽  
Extracellular Signal ◽  
Immunogenicity Assessment ◽  
Axon Bundle

Collagen VI (COL6) in the microenvironment was recently identified as an extracellular signal that bears the function of promoting orderly axon bundle formation. However, the large molecular weight of COL6 (≈2,000 kDa) limits its production and clinical application. It remains unclear whether the smaller subunit α chains of COL6 can exert axon bundling and ordering effects independently. Herein, based on a dorsal root ganglion (DRG) ex vivo model, the contributions of three main COL6 α chains on orderly nerve bundle formation were analyzed, and COL6 α2 showed the largest contribution weight. A recombinant COL6 α2 chain was produced and demonstrated to promote the formation of orderly axon bundles through the NCAM1-mediated pathway. The addition of COL6 α2 in conventional hydrogel triggered orderly nerve regeneration in a rat sciatic nerve defect model. Immunogenicity assessment showed weaker immunogenicity of COL6 α2 compared to that of the COL6 complex. These findings suggest that recombinant COL6 α2 is a promising material for orderly nerve regeneration.

scholarly journals Ex vivo MRI cell tracking of autologous mesenchymal stromal cells in an ovine osteochondral defect model

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hareklea Markides ◽  
Karin J. Newell ◽  
Heike Rudorf ◽  
Lia Blokpoel Ferreras ◽  
James E. Dixon ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Tracking ◽  
Osteochondral Defect ◽  
Ex Vivo ◽  
Defect Model

scholarly journals In Vivo Confocal Microscopy Evaluation in Patients with Keratoconus

2022 ◽  
Vol 11 (2) ◽  
pp. 393
Author(s):  
Alvin Wei Jun Teo ◽  
Hassan Mansoor ◽  
Nigel Sim ◽  
Molly Tzu-Yu Lin ◽  
Yu-Chi Liu
Keyword(s):  
Confocal Microscopy ◽  
Nerve Regeneration ◽  
Nerve Fibre ◽  
Ex Vivo ◽  
Fibre Length ◽  
In Vivo Confocal Microscopy ◽  
Corneal Sensitivity ◽  
Mechanical Removal ◽  
Cellular Changes

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients.

Fibronectin maintains survival of mouse natural killer (NK) cells via CD11b/Src/β-catenin pathway

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4081-4088 ◽  
Author(s):  
Ting Zhang ◽  
Shuxun Liu ◽  
Pengyuan Yang ◽  
Chaofeng Han ◽  
Jianli Wang ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nuclear Translocation ◽  
Nk Cell ◽  
Ex Vivo ◽  
Interleukin 12 ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
B Cell Leukemia

Abstract Tissue microenvironment and stroma-derived extracellular matrix (ECM) molecules play important roles in the survival and differentiation of cells. Mouse natural killer (NK) cells usually die within 24 hours once isolated ex vivo. Exogenous cytokines such as interleukin-12 (IL-12) and IL-15 are required to maintain the survival and activity of mouse NK cells cultured in vitro. Whether and how ECM molecules such as fibronectin can support the survival of NK cells remain unknown. We demonstrate that fibronectin, just like IL-15, can maintain survival of mouse NK cells in vitro. Furthermore, we show that fibronectin binds to the CD11b on NK cells, and then CD11b recruits and activates Src. Src can directly interact with β-catenin and trigger nuclear translocation of β-catenin. The activation of β-catenin promotes extracellular signal-related kinase (ERK) phosphorylation, resulting in the increased expression of antiapoptotic protein B-cell leukemia 2 (Bcl-2), which may contribute to the maintenance of NK-cell survival. Consistently, fibronectin cannot maintain the survival of CD11b− NK cells and β-catenin–deficient NK cells in vitro, and the number of NK cells is dramatically decreased in the β-catenin–deficient mice. Therefore, fibronectin can maintain survival of mouse NK cells by activating ERK and up-regulating Bcl-2 expression via CD11b/Src/β-catenin pathway.

scholarly journals Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal muscle

2001 ◽  
Vol 281 (2) ◽  
pp. R561-R571 ◽  
Author(s):  
Jennifer A. Wong ◽  
Aidar R. Gosmanov ◽  
Edward G. Schneider ◽  
Donald B. Thomason
Keyword(s):  
Skeletal Muscle ◽  
Atpase Activity ◽  
Insulin Treatment ◽  
Ex Vivo ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Significant Pathway ◽  
Stimulation Of

Na+-K+-Cl−cotransporter (NKCC) activity in quiescent skeletal muscle is modest. However, ex vivo stimulation of muscle for as little as 18 contractions (1 min, 0.3 Hz) dramatically increased the activity of the cotransporter, measured as the bumetanide-sensitive 86Rb influx, in both soleus and plantaris muscles. This activation of cotransporter activity remained relatively constant for up to 10-Hz stimulation for 1 min, falling off at higher frequencies (30-Hz stimulation for 1 min). Similarly, stimulation of skeletal muscle with adrenergic receptor agonists phenylephrine, isoproterenol, or epinephrine produced a dramatic stimulation of NKCC activity. It did not appear that stimulation of NKCC activity was a reflection of increased Na+-K+-ATPase activity because insulin treatment did not stimulate NKCC activity, despite insulin's well-known stimulation of Na+-K+-ATPase activity. Stimulation of NKCC activity could be blocked by pretreatment with inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) activity, indicating that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) MAPKs may be required. These data indicate a regulated NKCC activity in skeletal muscle that may provide a significant pathway for potassium transport into skeletal muscle fibers.

Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model

2014 ◽  
Vol 10 (10) ◽  
pp. 4197-4205 ◽  
Author(s):  
E.L. Smith ◽  
J.M. Kanczler ◽  
D. Gothard ◽  
C.A. Roberts ◽  
J.A. Wells ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Ex Vivo ◽  
Defect Model ◽  
Skeletal Tissue

scholarly journals Step training in a rat model for complex aneurysmal vascular microsurgery

2015 ◽  
Vol 29 (4) ◽  
pp. 493-502 ◽  
Author(s):  
Dan Martin ◽  
Mircea Radu Gorgan
Keyword(s):  
Nerve Regeneration ◽  
Ex Vivo ◽  
Nerve Repair ◽  
Training Model ◽  
Male Rats ◽  
Color Temperature ◽  
Brown Norway ◽  
Term Survival ◽  
Training Models

Abstract Introduction: Microsurgery training is a key step for the young neurosurgeons. Both in vascular and peripheral nerve pathology, microsurgical techniques are useful tools for the proper treatment. Many training models have been described, including ex vivo (chicken wings) and in vivo (rat, rabbit) ones. Complex microsurgery training include termino-terminal vessel anastomosis and nerve repair. The aim of this study was to describe a reproducible complex microsurgery training model in rats. Materials and methods: The experimental animals were Brown Norway male rats between 10-16 weeks (average 13) and weighing between 250-400g (average 320g). We performed n=10 rat hind limb replantations. The surgical steps and preoperative management are carefully described. We evaluated the vascular patency by clinical assessment-color, temperature, capillary refill. The rats were daily inspected for any signs of infections. The nerve regeneration was assessed by foot print method. Results: There were no case of vascular compromise or autophagia. All rats had long term survival (>90 days). The nerve regeneration was clinically completed at 6 months postoperative. The mean operative time was 183 minutes, and ischemia time was 25 minutes.

scholarly journals Ex-Vivo Stimulation of Adipose Stem Cells by Growth Factors and Fibrin-Hydrogel Assisted Delivery Strategies for Treating Nerve Gap-Injuries

2020 ◽  
Vol 7 (2) ◽  
pp. 42
Author(s):  
Katharina M. Prautsch ◽  
Lucas Degrugillier ◽  
Dirk J. Schaefer ◽  
Raphael Guzman ◽  
Daniel F. Kalbermatten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Nerve Regeneration ◽  
Ex Vivo ◽  
Axonal Outgrowth ◽  
Assisted Delivery ◽  
Delivery Strategies ◽  
Stimulation Of

Peripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-vivo stimulation of ASC by using growth factors, i.e., nerve growth factor (NGF) or vascular endothelial growth factor (VEGF) and secondly on fibrin-hydrogel nerve conduits (FNC) assisted ASC delivery strategies, i.e., intramural vs. intraluminal loading. ASC were stimulated by NGF or VEGF for 3 days and the resulting secretome was subsequently evaluated in an in vitro axonal outgrowth assay. For the animal study, a 10 mm sciatic nerve gap-injury was created in rats and reconstructed using FNC loaded with ASC. Secretome derived from NGF-stimulated ASC promoted significant axonal outgrowth from the DRG-explants in comparison to all other conditions. Thus, NGF-stimulated ASC were further investigated in animals and found to enhance early nerve regeneration as evidenced by the increased number of β-Tubulin III+ axons. Notably, FNC assisted intramural delivery enabled the improvement of ASC’s therapeutic efficacy in comparison to the intraluminal delivery system. Thus, ex-vivo stimulation of ASC by NGF and FNC assisted intramural delivery may offer new options for developing effective therapies.

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