Regenerative Medicine of the Trachea: The First Human Case

2005 ◽  
Vol 114 (6) ◽  
pp. 429-433 ◽  
Author(s):  
Koichi Omori ◽  
Tatsuo Nakamura ◽  
Shinichi Kanemaru ◽  
Ryo Asato ◽  
Masaru Yamashita ◽  
...  

Objectives: The objective of the present study was to demonstrate regenerative medicine of the tracheal tissue by using an in situ tissue engineering technique for airway reconstruction. Methods: Based on the previous successful experimental animal studies, the current regenerative technique was applied to repair of the trachea of a 78-year-old woman with thyroid cancer. A Marlex mesh tube covered by collagen sponge was used as a tissue scaffold. The operative intervention included right hemithyroidectomy, resection of the trachea, and tracheoplasty using the scaffold. The right half of three rings of the trachea was resected, and the scaffold material was sutured to the defect of the trachea. Results: After 2 weeks, the mesh collagen structure of the artificial material could be seen with endoscopy in most of the implanted area. The artificial material was covered with epithelial growth after 2 months. Epithelialization continued to cover the artificial material completely for 2 years without any complications. Conclusions: The current regenerative technique avoided tracheotomy, a second operation, and deformity. Good epithelialization has been observed on the tracheal luminal surface without any complications for 2 years. Although long-term observation is required, regenerative medicine of the tracheal tissue appears feasible for airway reconstruction.

2021 ◽  
pp. 62-67
Author(s):  
Annegret Abaza ◽  
Özlem Dikmetas ◽  
Irmingard Neuhann ◽  
Faik Gelisken

We report a case of posterior uveal effusion (UE) with a long-term follow-up that has occurred following cataract surgery. A 64-year-old woman presented with diminished vision of the right eye (RE) 3 weeks after an uneventful phacoemulsification and intraocular lens implantation. Complete ophthalmic examination including fluorescein angiography (FA), indocyanine green angiography (ICGA), echography and optical coherence tomography (OCT) were performed. Best corrected visual acuity (BCVA) of the RE was 20/50. Anterior segment and intraocular pressure were unremarkable. OCT revealed prominent folds of the choroid and retina, subretinal fluid and darkening of the choroid with reduced visibility of the choroidal vessels and the scleral border. The left eye (LE) was unremarkable. BCVA of the LE was: 20/20. After topical anti-inflammatory and systemic corticosteroid therapy for 5 months, no morphological change of the macula was seen. The patient was observed without any treatment. Forty-three months after the cataract surgery and 38 months after cessation of the corticosteroid therapy, OCT revealed a normal macular morphology and the BCVA improved to 20/25. Even though rare, UE at the posterior pole may occur after modern cataract surgery. OCT examination is a reliable tool in monitoring the macular morphology. Since morphological and functional improvement can be seen in long-term, observation may be considered for some cases of posterior UE with resistance to the therapy.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1483
Author(s):  
Margarita Calonge ◽  
Teresa Nieto-Miguel ◽  
Ana de la Mata ◽  
Sara Galindo ◽  
José M. Herreras ◽  
...  

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.


2020 ◽  
Vol 10 (4) ◽  
pp. 490-501
Author(s):  
Mozhgan Jahani ◽  
Davood Rezazadeh ◽  
Parisa Mohammadi ◽  
Amir Abdolmaleki ◽  
Amir Norooznezhad ◽  
...  

Blood vessel development is one of the most prominent steps in regenerative medicine due tothe restoration of blood flow to the ischemic tissues and providing the rapid vascularizationin clinical-sized tissue-engineered grafts. However, currently tissue engineering technique isrestricted because of the inadequate in vitro/in vivo tissue vascularization. Some challenges likeas transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit theprogression of vessels in smaller than clinically relevant dimensions as well in vivo integration.In this regard, the scholars attempted to promote the vascularization process relied on the stemcells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of themto enable the emergence of ideal microenvironment which is needed for treatment of unhealthyorgans or tissue regeneration and formation of new blood vessels. Thus, in the present reviewwe aim to describe these approaches, advances, obstacles and opportunities as well as theirapplication in regeneration of heart as a prominent angiogenesis-dependent organ.


1997 ◽  
Vol 20 (1) ◽  
pp. 51-59 ◽  
Author(s):  
JOHN K. TRIEDMAN ◽  
KATHY J. JENKINS ◽  
STEVEN D. COLAN ◽  
RICHARD PRAAGH ◽  
JAMES E. LOCK ◽  
...  

2005 ◽  
Vol 284-286 ◽  
pp. 643-646 ◽  
Author(s):  
Elizabeth C. Kolos ◽  
Andrew Ruys ◽  
Ramin Rohanizadeh ◽  
M.M. Muir ◽  
Greg J. Roger

The aim of this study was to fabricate a micro-tube scaffold using a biomimetic method (immersion in Simulated Body Fluid, SBF) to coat apatite on cotton fibres. The cotton fibres were first pre-treated using a phosphorylation technique and then apatite crystals were deposited on the fibres by immersing in SBF. Micro-tubes were then formed by burning out the cotton fibres at various temperatures between 950-1250°C. The scaffolds were fabricated by compaction of the micro-tubes in a mould. The compacted micro-tubes were then sintered at various temperatures between 900-1200°C. The biocompatibility and the effects of the surface morphology of scaffolds on cell coverage and proliferation were determined using osteoblast cell culture. The results showed that these scaddolds were biocompatible and able to support cell growth. Future studies include animal studies for biomimetic tissue scaffold as a bone filler substitute material.


2007 ◽  
Vol 19 (6) ◽  
pp. 1033-1049 ◽  
Author(s):  
Andrea Di Ferdinando ◽  
Domenico Parisi ◽  
Paolo Bartolomeo

Computational modeling is a useful tool for spelling out hypotheses in cognitive neuroscience and testing their predictions in artificial systems. Here we describe a series of simulations involving neural networks that learned to perform their task by self-organizing their internal connections. The networks controlled artificial agents with an orienting eye and an arm. Agents saw objects with various shapes and locations and learned to press a key appropriate to their shape. The results showed the following: (1) Despite being able to see the entire visual scene without moving their eye, agents learned to orient their eye toward a peripherally presented object. (2) Neural networks whose hidden layers were previously partitioned into units dedicated to eye orienting and units dedicated to arm movements learned the identification task faster and more accurately than did nonmodular networks. (3) Nonetheless, even nonmodular networks developed a similar functional segregation through self-organization of their hidden layer. (4) After partial disconnection of the hidden layer from the input layer, the lesioned agents continued to respond accurately to single stimuli, wherever they occurred, but on double simultaneous stimulation they oriented toward and responded only to the right-sided stimulus, thus simulating extinction/neglect. These results stress the generality of the advantages provided by orienting processes. Hard-wired modularity, reminiscent of the distinct cortical visual streams in the primate brain, provided further evolutionary advantages. Finally, disconnection is likely to be a mechanism of primary importance in the pathogenesis of neglect and extinction symptoms, consistent with recent evidence from animal studies and brain-damaged patients.


2012 ◽  
Vol 24 (3) ◽  
pp. 588-599 ◽  
Author(s):  
Matthijs G. Bossong ◽  
Gerry Jager ◽  
Hendrika H. van Hell ◽  
Lineke Zuurman ◽  
J. Martijn Jansma ◽  
...  

Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.


2020 ◽  
Vol 11 (4) ◽  
pp. 6079-6084
Author(s):  
Katharigatta N. Venugopala

Identifying the right dose is arguably an essential step in the design of experiments related to drug discovery and development. Often, dose extrapolation is done to scale the doses of a drug from one species to another. However, literature is replete with cases that warrant against the careless and inadequate application of dose-extrapolation methodologies. Increasing costs of research and the development and ethical considerations of experimentation in animals and humans do not condone injudicious design of experiments. This call to caution forms the essential premise of the current review, which focuses on the methodology of the dose extrapolation and its place in early-phase clinical trials and animal studies. Furthermore, the review also provides an update on within-species dose extrapolation to address the issues of adapting adult human doses to pediatric and geriatric settings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angharad N. de Cates ◽  
Lucy C. Wright ◽  
Marieke A. G. Martens ◽  
Daisy Gibson ◽  
Cagdas Türkmen ◽  
...  

AbstractCognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.


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