Isolated bilateral transverse agenesis of the distal segments of the lower limbs at the level of the knee joint in a human fetus.

Congenital limb anomalies occur in Europe with a prevalence of 3.81/1,000 births and can have a major impact on patients and their families. The present study concerned a female fetus aborted at 23 weeks of gestation because she was affected by non-syndromic bilateral absence of the zeugopod (leg) and autopod (foot). Autopsy of the aborted fetus, X-ray imaging, MRI, and histochemical analysis showed that the distal extremity of both femurs was continued by a cartilage-like mass, without joint cavitation. Karyotype was normal. Moreover, no damaging variant was detected by exome sequencing. The limb characteristics of the fetus, which to our knowledge have not yet been reported in humans, suggest a developmental arrest similar to anomalies described in chicks following surgical experiments on the apical ectodermal ridge of the lower limbs.

Collagen molecular organization preservation in human fascia lata and periosteum after tissue engineering.

Large bone defect regeneration remains a major challenge for orthopedic surgeons. Tissue engineering approaches are therefore emerging in order to overcome this limitation. However, these processes can alter some of essential native tissue properties such as intermolecular crosslinks of collagen triple helices, which are known for their essential role in tissue structure and function. We assessed the persistence of extracellular matrix (ECM) properties in human fascia lata (HFL) and periosteum (HP) after tissue engineering processes such as decellularization and sterilization. Harvested from cadaveric donors (N = 3), samples from each HFL and HP were decellularized following five different chemical protocols with and without detergents (D1-D4 and D5, respectively). D1 to D4 consisted of different combinations of Triton, Sodium dodecyl sulfate and Deoxyribonuclease, while D5 is routinely used in the institutional tissue bank. Decellularized HFL tissues were further gamma-irradiated (minimum 25 kGy) in order to study the impact of sterilization on the ECM. Polarized light microscopy (PLM) was used to estimate the thickness and density of collagen fibers. Tissue hydration and content of hydroxyproline, enzymatic crosslinks, and non-enzymatic crosslinks (pentosidine) were semi-quantified with Raman spectroscopy. ELISA was also used to analyze the maintenance of the decorin (DCN), an important small leucine rich proteoglycan for fibrillogenesis. Among the decellularization protocols, detergent-free treatments tended to further disorganize HFL samples, as more thin fibers (+53.7%) and less thick ones (-32.6%) were recorded, as well as less collagen enzymatic crosslinks (-25.2%, p = 0.19) and a significant decrease of DCN (p = 0.036). GAG content was significantly reduced in both tissue types after all decellularization protocols. On the other hand, HP samples were more sensitive to the D1 detergent-based treatments, with more disrupted collagen organization and greater, though not significant loss of enzymatic crosslinks (-37.4%, p = 0.137). Irradiation of D5 HFL samples, led to a further and significant loss in the content of enzymatic crosslinks (-29.4%, p = 0.037) than what was observed with the decellularization process. Overall, the results suggest that the decellularization processes did not significantly alter the matrix. However, the addition of a gamma-irradiation is deleterious to the collagen structural integrity of the tissue.

Molecular study of a Hoxa2 gain-of-function in chondrogenesis: a model of idiopathic proportionate short stature.

In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions, our results give an insight into understanding proportionate short stature pathogenesis by highlighting molecular factors whose combined deregulation may be involved in such a disease.

Face graft? Extrapolation of facial allotransplantation to children.

The possibility to imagine a vascularized composite allotransplantation for disfigured children is felt more critical than for adults non on technical point of view but in terms of indications and justifications. The question is not about surgery. It is related to the pathologies themselves for which transplant could be suitable. Moreover the procurement of face transplant will be more difficult because of immunologic criteria but also age and phototype. Specificity of the newborn malformative face is usually not only a question of tissue defect. It is reasonably not an indication for VCA. It should be added that nothing is known about the future of transplantation in terms of duration but also morbidities due to immunosuppression. Indications are rather negative. To rise the question of VCA for children has a double benefit. The first is to point out that surgical innovation often arise from a non imaginable or non imagined clinical situation. The second is the question of VCA in newborn regarding the tolerance.

Polygonal deformation of the dural sac in lumbar epidural lipomatosis: anatomic explanation by the presence of meningovertebral ligaments.

BACKGROUND AND PURPOSE: In patients with epidural lipomatosis, axial lumbar spine CT and MR images occasionally reveal a geometric, polygonal or stellar, shape of the dural sac. The purpose of this study was to define the anatomic structures responsible for this radiologic appearance. We hypothesized that meningovertebral ligaments could anchor the dura mater to the osteofibrous walls of the spinal canal and account for the geometric deformation of the dural sac. METHODS: The epidural spaces were examined in 15 adult cadaveric and seven aborted fetal lumbar spines. For macroscopic studies, 70 adult vertebral segments were separated and dissected by removing the extradural fat. For microscopic examination, axial histologic sections were obtained from 35 fetal and five adult undissected vertebral segments. RESULTS: Meningovertebral ligaments were observed in the median, paramedian, and lateral aspects of the anterior and posterior epidural spaces of both adult and fetal lumbar spines. These ligaments anchor the outer surface of the dura mater to the osteofibrous walls of the lumbar canal. They may form an irregular longitudinal septum partitioning the epidural space. Histologic examination demonstrated the fibroelastic composition of these ligaments and suggested their possible perivascular morphogenetic origin. CONCLUSION: The morphologic and topographic features of the meningovertebral ligaments explain the polygonal, stellar, or Y-shaped deformation of the dural sac observed on axial CT and MR images in patients with lumbar epidural lipomatosis.

Arguing the ethics of facial transplantation.

While 7 face transplants have been performed around the world, to date, there remains debate regarding the validity of this procedure. We submit that performing a facial transplant-in the appropriately selected patient-is technically defensible and ethically sound. By outlining the technical and ethical boundaries of the debate, responding to the key arguments against the procedure, and describing its motivations and potential benefits, we state our justification of facial transplantation.

Current concepts and future challenges in facial transplantation.

Facial allotransplantation has become a surgical reality. The first successful segmental human face transplants have demonstrated that facial allografts are reliable, their rejection can be prevented by low-dose immunosuppression, and their neurologic recovery enables oral and expressive functions of the face to be restored. Clinical facts have shown that the risk-benefit balance is acceptable in the medium term, that at the neurocognitive level the allograft is reintegrated in the body scheme of the recipient, and that it does not engender a donor identity transfer. This article presents a classification of facial allografts and discusses the technical, immunologic, and ethical challenges that lie ahead.