Strands Of Connective Tissue Research Articles

A rare variation of intrinsic and extrinsic hand muscles represented by a bi-ventered first lumbrical extending into the carpal tunnel combined with bilateral fifth superficial flexor digitorum tendon regression

A rare unilateral variation of the first left lumbrical muscle was discovered in a female Caucasian cadaver dissected during a first year anatomy course at the Paracelsus Medical University - Nuremberg, Germany. The muscle possessed two venters with the first originating near the medial epicondyle of the humerus together with the intramuscular tendon of the superficial flexor digitorum tendon, and the second presenting as a regular first lumbrical muscle with radial palmar origin from first tendon of the deep flexor digitorum muscle. Both muscle bellies were connected by a 1.42mm thick tendon that passed beneath the median nerve and ran through the carpal tunnel. The second belly was enlarged and entered the distal part of the carpal tunnel. Interestingly, the donor revealed further rare variations such as a bilateral regression of the fifth superficial flexor tendons to an obviously non functional connective tissue strand, lack of both palmaris longus muscles, a discoid lateral meniscus in the left knee, and reduction of the plantaris muscle to a fascia-like structure on the right leg. Lumbrical muscle variations extending into the carpal tunnel, especially those associated with auxiliary tendons, have significant clinical relevance due to their association with carpal tunnel syndrome.

Fascia glutealis as mediator of musculocutaneous dynamics in the buttocks region

Cellulite is a change of the skin and subcutaneous tissue that develops mainly in the thighs and gluteal region of almost all women. Many concepts in the pathological physiology of cellulite are to some extent contradictory and inconclusive; however, some studies point to structural changes in the dermis and subcutaneous tissue. A correlation of cellulite with focal hypertrophic subcutaneous connective tissue strands and lower density of connective tissue septa in subcutaneous tissue also point to changes in the related gluteal fascia and thus in the closely interlaced gluteal muscles. A rapid degenerative development of the muscle dynamics that were originally gained over generations unquestionably occurs in the Caucasian race and its related urbanization. The gender-specific dimorphism in the subcutaneous area must also be investigated further, since almost exclusively women are affected. For this reason we have anatomically examined male and female gluteal zones and demonstrated significant genderspecific changes. In particular, a weakening of the muscle-tendon and muscle-fascia dynamics of the gluteal muscles appears to be responsible for the round, superficially visible dermal changes. The entire embryonic unit of the muscle-fascia-skin structures in the buttocks and thigh area is involved in female cellulite. A transformation of these degenerative changes through regenerative measures, such as active movement and shock wave therapy is, therefore, appropriate and necessary.

Experimental-morphological justification of the effectiveness for the connective tissue carcass formation in the anterior abdominal wall depending on the topographic-anatomical graft implant location

The aim — to study morphometric characteristics of the formation of connective tissue skeleton, depending on the location of the mesh between the different anatomical structures of the anterior abdominal wall.Materials and methods. An experiment was performed with 30 adult chinchilla rabbits, which had undergone implantation of a polypropylene mesh sterile pieces (PROLEN, Ethicon) of size 1.0 ´ 1.0 cm in the anterior abdominal wall lateral area. All studied animals were divided into 3 groups depending on the place of the mesh implantation: preperitoneal (n = 10), intramuscular (n = 10) and subaponeurotic (n = 10). The tissues of the anterior abdominal wall sized 1.5 ´ 1.5 cm were sampled on the 7th, 14th, 21st, 28th and 35th day after implantation. To assess the effectiveness of the connective tissue framework formation, depending on the topographic location of the implant, a morphometric study with following parameters was performed: relative area of collagen fibers, relative amount of collagen fibers with a fiber thickness more than 10 µm and less than 10 µm, the relative area of the cell component.Results and discussion. It was established that the scar tissue formation after the mesh implantation has significant differences depending on its localization. In the area of the peritoneum and the muscle the mesh implantation induced reactive changes, manifested by granulation tissue formation, rich by non­differentiable vessels, the structure of which fibrocytes and fibroblasts was dominated. Up to 21 day the connective tissue scar is formed from dense bundles of collagen fibrils. Up to 28th — 35th day a further connective tissue maturation processed, fibroblasts number reduced, the fibrous structures number increased. The mesh threads were embedded in connective tissue fibers, the strands of mature connective tissue formed between the threads, but thinner than in the filaments locations. Aponeurotic mesh implantation caused a somewhat different reaction. The signs of edema and the fibrous structures formation around and between the threads were expressed on the 7th day in the aponeurosis area. A solid layer of mature connective tissue with a large fibers and fibroblasts number was formed on the 21st day. The thickness of the scar was 5 — 6 times higher than in the muscle and peritoneum. The predominance of the fibrillar component of scar tissue over the cell, mature collagen fibers over the young fibrous structures was observed on the 21st day of the experiment, that confirmed the earlier initiation and high rate of peri­implant reparative­proliferative processes for the subaponeurotic mesh implant in comparison with preperitoneal and intermuscular ones.Conclusions. The obtained experimental data allow to postulate a better morphometric and histological characteristic of the scar formation in case of subaponeurotic mesh placement that is important for the surgical approach choice. The study results substantiate the morphological improvement of existing treatment methods in patients with a considerable distraction of aponeurotic edges with postoperative ventral hernias, as a remote complications of gunshot peritonitis surgical treatment.

Pituitary adenoma in aged rats. A case report

The prevalence of neoplastic disease in the rat is well defined, because this species has been routinely used for decades in large-scale carcinogenic, aging and toxicological studies. Stock and strain-specific differences in the prevalence of some types of tumors are well documented. Pituitary adenoma is a neoplastic lesion which can be observed in older or aged rats of both sexes. In addition to sex, strain, diet, genetic factor, breeding history and accommodation may also play a role. Pituitary adenoma can also affect hamster, guinea pig and mice. The aim of this article is to report an incidence of pituitary adenomas, which was observed in a rat breeding colony of the Center for Experimental Surgery of the Biomedical Research Foundation of the Academy of Athens. During the clinical examination five female Wistar rats, at the age of 18 to 24 months old, expressed anorexia, weight loss, ataxia and bilateral blindness. At necropsy, the pituitary gland was enlarged with lobulations, often dark red to brown and hemorrhagic in appearance. In some cases there was a marked compression of the overlying mesencephalon. Histological examination with haematoxylin-eosin were observed cords and nests of glandular cells bound by strands of connective tissue, with an abundant capillary network. On immunohistochemical examination were observed strong positive reaction of synaptophysin. Findings were similar to pituitary adenoma. Pituitary adenoma is a serious non-reversible disease leading to the death of the animal. Laboratory animals with pituitary adenomas can be used as models in research of human pituitary adenoma.

The Distribution and Structure of the Microvasculature of the Phallus in the Ostrich (Struthio camelus)

Abstract This study determined the distribution and specialized morphology (gaps and fenestrations, irregular endothelium, internalization of luminal material) of vessels in the spongy and erectile tissue of the phallus in the ostrich. Specimens from the phallus harvested from 18 sexual mature and active ostriches were utilized. General routine fixation was used for tissue blocks and then they were processed conventionally for observation under the Transmission Electron Microscope (TEM). The spongy tissue in the root of the phallus exhibited several blood vessels (mainly venules) within connective tissue strands. The capillaries displayed thick and attenuated endothelial profiles, whereas the venules were lined with an attenuated endothelium. Both vessel types displayed fenestrations and prominent gaps supported by a continuation of the basal lamina. Numerous cytoplasmic processes extended from the capillary endothelium, in places appearing to enclose and sequestrate luminal contents by phagocytosis. The internalized material appeared in the form of relatively large, pale vesicles. The endothelium was extremely irregular in profile, in some instances appearing to be composed of more than one layer of squamous cells. The erectile tissue lining the phallic sulcus presented relatively few capillaries and venules. These vessels exhibited features similar to those seen in the spongy tissue but the endothelial cells were markedly more complex and irregular in design.

Synovial incorporation of polyacrylamide hydrogel after injection into normal and osteoarthritic animal joints

Polyacrylamide hydrogel (PAAG) is a non-toxic, non-degradable synthetic product, used for years in the augmentation of soft tissues. Preliminary results in animals and humans have suggested long-lasting beneficial effects on symptoms of osteoarthritis (OA). The aim of this histopathological study was to investigate whether intra-articular injection of PAAG is integrated into synovial tissue in normal and OA animal joints, and if this integration is sustained. (A) A prospective, controlled, longitudinal study of normal knee joints injected with PAAG was performed in 10 rabbits, following the animals up to 1 year, and (B) a post mortem examination was carried out up to 2 years post-injection on 18 horse joints which had previously been treated with 1-2 injections of 2ml PAAG for clinically and radiologically diagnosed OA. Integration of the injected gel was evident at day 10 in the rabbit and by day 14 in the horse, with proliferation and invasion of synovial cells into the gel. By day 90 in rabbit joints and day 30 in horse joints, the gel had formed a sub-synovial layer, which was traversed by thin strands of connective tissue with vessels and covered by a synovial lining facing the joint cavity. This histological appearance persisted up to 2 years post-injection in horse joints. Intra-articular injection of PAAG results in a stable, long-lasting sub-synovial layer of gel traversed with thin strands of connective tissue. Further studies to explore potential effects on synovial inflammation and pain are warranted.

Fibrosis: a structural modulator of sinoatrial node physiology and dysfunction.

Heart rhythm is initialized and controlled by the Sinoatrial Node (SAN), the primary pacemaker of the heart. The SAN is a heterogeneous multi-compartment structure characterized by clusters of specialized cardiomyocytes enmeshed within strands of connective tissue or fibrosis. Intranodal fibrosis is emerging as an important modulator of structural and functional integrity of the SAN pacemaker complex. In adult human hearts, fatty tissue and fibrosis insulate the SAN from the hyperpolarizing effect of the surrounding atria while electrical communication between the SAN and right atrium is restricted to discrete SAN conduction pathways. The amount of fibrosis within the SAN is inversely correlated with heart rate, while age and heart size are positively correlated with fibrosis. Pathological upregulation of fibrosis within the SAN may lead to tachycardia-bradycardia arrhythmias and cardiac arrest, possibly due to SAN reentry and exit block, and is associated with atrial fibrillation, ventricular arrhythmias, heart failure and myocardial infarction. In this review, we will discuss current literature on the role of fibrosis in normal SAN structure and function, as well as the causes and consequences of SAN fibrosis upregulation in disease conditions.

A case report of sebaceous gland adenocarcinoma in a dog

Pathological diagnosis of a surgically excised sebaceous adenocarcinoma in a 6 year old male non-descript dog is being reported here. The animal turned up with an ulcerated mass on the dorsum. Fine Needle Aspiration Cytology suggested tumour owing to cells of higher nucleus-cytoplasmic ratio. The animal was subjected to surgery and from the excised mass, specimen was collected and subjected to histopathological study. The exteriorized mass weighed 60 grams. Histopathology revealed proliferating sheets of cells with large vesicular nucleus with indistinct boundaries which formed papillary projections. Some of them formed glandular pattern with multiple layer of cells separated into lobules by narrow strands of connective tissue and occasional fibrous tissue proliferation. Neutrophil and mononuclear cell infiltrations were also found. The glandular lining cells were hyperchromatic and mitotic figures were evident. Based on the histopathological features, the tumour was confirmed to be sebaceous adenocarcinoma.

Porcine Dermis-Derived Collagen Membranes Induce Implantation Bed Vascularization Via Multinucleated Giant Cells: A Physiological Reaction?

In this study, the tissue reactions to 2 new porcine dermis-derived collagen membranes of different thickness were analyzed. The thicker material (Mucoderm) contained sporadically preexisting vessel skeletons and fatty islands. The thinner membrane (Collprotect) had a bilayered structure (porous and occlusive side) without any preexisting structures. These materials were implanted subcutaneously in mice to analyze the tissue reactions and potential transmembranous vascularization. Histological and histomorphometrical methodologies were performed at 4 time points (3, 10, 15, and 30 days). Both materials permitted stepwise connective tissue ingrowth into their central regions. In the Mucoderm matrix, newly built microvessels were found within the preexisting vessel and fatty island skeletons after 30 days. This vascularization was independent of the inflammation-related vascularization on both material surfaces. The Collprotect membrane underwent material disintegration by connective tissue strands in combination with vessels and multinucleated giant cells. The histomorphometric analyses revealed that the thickness of Mucoderm did not decrease significantly, while an initial significant decrease of membrane thickness in the case of Collprotect was found at day 15. The present results demonstrate that the 2 analyzed collagen membranes underwent a multinucleated giant cell-associated vascularization. Neither of the materials underwent transmembraneous vascularization. The microvessels were found within the preexisting vessel and fatty island skeletons. Additional long-term studies and clinical studies are necessary to determine how the observed foreign body giant cells affect tissue regeneration.

English

Introduction Angiokeratoma is a broad term that describes various conditions of asymptomatic hyperkeratotic vascular disorders with a histologic combination of hyperkeratosis and superficial dermal vascular ectasia. Here we are describing a case of recurrent angiokeratoma scroti. Case report A 34-year-old patient presented to the surgery department with multiple small papules over the scrotum with a previous history of two recurrences. They were slowly progressive, itchy and not associated with any bleeding. Examination revealed multiple soft compressible papules of 3–4 mm diameter with excoriation marks. Systemic examination and routine investigations were normal. Histologically, they were composed of numerous dilated thin walled congested capillaries mainly in the papillary dermis. Epidermis revealed variable degree of acanthosis and elongation of rete ridges and mild hyperkeratosis. Electrocauterisation of lesions was done and the follow-up period of three months was uneventful. Conclusion Although angiokeratoma scroti is not an uncommon entity, good treatment modality with minimal adverse effects in terms of complete resolution of diffuse lesions, recurrence, scarring, crusting, bleeding or cosmetic results is still not available. Introduction The term angiokeratoma is used to describe several distinct entities characterised by vascular nodules in the skin, with a histological picture of dermal vascular ectasia surmounted by hyperkeratosis of the epidermis. Angiokeratoma of the scrotum was originally described by Fordyce in 18961 reporting a case of 60-year-old man with multiple warty lesions confined to the scrotum only. Only a few cases of recurrent angiokeratoma had been reported since then. We describe here an adult male presenting with multiple papules over the scrotum with a previous history of two recurrences. Case report A 34-year-old male presented in the surgery department with moderate itching and multiple papules arranged diffusely over the scrotum. There was history of two recurrences five and three years back with the same complaints. Electrocauterisation of lesions was previously done two times, although no previous pathological reports were available. Each time, the follow-up period of four to six months had been uneventful. Even after complete post-operative healing, the patient continued to experience persistent discomfort, pruritis and psychological distress. Mere contact of the affected area with his underwear resulted in constant irritation. There was no history of trauma, episodic bleeding, similar lesions somewhere else on his body, inguinal hernia, genitourinary tumours, thrombophlebitis or varicocele. Physical examination revealed multiple, soft, bluish-red, compressible papules of 3–4 mm diameter with excoriation marks and focal thickening of skin, which might be due to previous surgical intervention. Systemic examination and routine investigations including urine examination and ultrasonography of scrotum were unremarkable. This time also, lesions were electrocauterised and excised biopsy tissue, consisting of multiple greyish white pieces of soft tissue measuring together 1.3 × 1.0 cm., was sent for histopathological examination to the pathology department. The whole tissue was processed. The biopsy submitted was stained with haematoxylin and eosin and revealed epidermis with mild hyperkeratosis, variable degree of acanthosis and elongation of rete ridges. Papillary dermis showed numerous dilated thin-walled congested capillaries in small groups separated by thin strands of connective tissue. Histology established the diagnosis of angiokeratoma of scrotum. Follow-up period of three months to assess the cosmetic result and to look for recurrences was uneventful. Discussion Patients of angiokeratoma usually present with small, bright red, vascular papules rarely larger than 3–4 mm. Angiokeratoma of scrotum are true ectasia of blood vessels. Initially, the lesions may be red, soft and compressible but later on may be firm, keratotic and sometimes warty2. These vascular lesions may be single and discrete or arranged in clusters. The most frequent symptom is a sensation of heaviness, tension in the scrotum accompanied by irritation along with bleeding of varying degree and superadded infection. Progressive worsening of symptoms, extension of the involved area, repeated episodes of cellulitis and infection cause psychological and emotional distress in the patient; sometimes requiring hospitalisation. * Corresponding author Email: drbrijeshthakur03@gmail.com NIIMS University, Jaipur, India

Internal receptors in insect appendages project directly into a special brain neuropile

BackgroundThe great majority of afferent neurons of insect legs project into their segmental ganglion. Intersegmental projections are rare and are only formed by sense organs associated with the basal joints of the legs. Such intersegmental projections never ascend as far as the brain and they form extensive ramifications within thoracic ganglia. A few afferents of chordotonal organs of the subcoxal joints ascend as far as the suboesophageal ganglion.ResultsWe describe novel afferent neurons in distal segments of locust legs that project directly into the brain without forming ramifications in other ganglia. In the brain, the fibres terminate with characteristic terminals in a small neuropile previously named the superficial ventral inferior protocerebrum. The somata of these neurons are located in the tibiae and tarsi of all legs and they are located within branches of peripheral nerves, or closely associated with such branches. They are not associated with any accessory structures such as tendons or connective tissue strands as typical for insect internal mechanoreceptors such as chordotonal organs or stretch receptors. Morphologically they show great similarity to certain insect infrared receptors.We could not observe projections into the superficial ventral inferior protocerebrum after staining mandibular or labial nerves, but we confirm previous studies that showed projections into the same brain neuropile after staining maxillary and antennal nerves, indicating that most likely similar neurons are present in these appendages also.ConclusionBecause of their location deep within the lumen of appendages the function of these neurons as infrared receptors is unlikely. Their projection pattern and other morphological features indicate that the neurons convey information about an internal physiological parameter directly into a special brain neuropile. We discuss their possible function as thermoreceptors.

Blood parameters in female Zandi lambs as affected by liver biopsy methodology

The aim of the present study was to investigate the normal blood parameters of Iranian fat-tailed sheep (Zandi) and their changes due to rapid liver biopsy technique with a tru-cut biopsy needle. In ten ewe lambs, blood samples were collected from jugular vein and biopsy needle was inserted through the dorsal one third of the 11th intercostal space, on the right hand side of the lambs and liver specimen was collected. Physical examinations were performed on alternate days during the experiment. Blood collection was done on both before (day1) and after (day17) the biopsy. All animals were slaughtered at day17. Values were compared using paired t test. While biopsy did not make any significant changes in mean values of body temperature, heart rate, respiratory rate, PCV, WBC, neutrophil, lymphocyte, eosinophil, monocyte, total serum protein, AST, ALT, and serum calcium (p > 0.05), it made a significant difference on the values of ALP (p < 0.001), serum inorganic phosphate (p = 0.035), and magnesium (p = 0.013). Necropsy examination revealed the points of hitting the biopsy needles on the diaphragmatic surface of the livers, surrounded by a zone of intense hyperemia. Peritoneal adhesions accompanying with typical strands of fibrous connective tissue between diaphragmatic surface of the liver and adjacent abdominal wall were found in two cases.

Four‐dimensional analysis of early pelvic girdle development in Rana temporaria

A key event in vertebrate evolution is the linkage of the appendicular to the axial skeleton. The present study investigates the developmental dynamics of pelvic girdle morphogenesis in Rana temporaria up until metamorphosis, with respect to its functional and spatio-temporal organization. The main questions to be addressed are: initial location and the number of elements contributing to pelvic girdle formation, mechanism of bridging between the pelvic anlage and the sacrum and arthrogenesis. Serial histological sections of specimens from Gosner Stages 30 to 41 were bright-field microscopically examined and 3D-reconstructed. 3D-models were merged to 4D-animations illustrating the complex developmental dynamics through time. The results reveal the initial formation of a single mesenchymal condensation located close to the appendicular skeleton, but far from the axial skeleton. In addition, our analysis detects a thin connective tissue strand in R. temporaria guiding the elongation of the ilium towards the sacrum. The 4D-visualization allows novel insight into the ilio-sacral bridging process and the reorientation of the pelvis.

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes

String vessels are thin connective tissue strands, remnants of capillaries, with no endothelial cells; they do not carry blood flow. They occur in numerous species, particularly in the central nervous system, but can occur in any tissue where capillaries have died. String vessels are often associated with pathologies such as Alzheimer's disease, ischemia, and irradiation, but are also found in normal human brains from preterm babies to the aged. They provide a record of the original blood vessel location, but gradually disappear after months or years. There have been numerous studies of string vessels (acellular capillaries) in the retina, because retinal vessels can be seen in great detail in whole mounts after trypsin digestion. Capillary regression occurs by apoptosis, synchronously along capillary segments, with macrophages engulfing apoptotic endothelial cells. Macrophages may cause the apoptosis, or the regression may be triggered by loss of the endothelial cell survival factor VEGF. VEGF expression is induced by hypoxia and promotes capillary growth. Cessation of blood flow eliminates the shear stress that helps maintain endothelial cell survival. Capillaries can re-grow by proliferation and migration of endothelial cells into empty basement membrane tubes, which provide a structural scaffold, replete with signaling molecules. This is a problem in tumor control, but useful for recovery from capillary loss. There is an age-related waning of VEGF expression in response to hypoxia. This causes an age-related decline in cerebral angiogenesis and results in neuronal loss. It may also contribute to the proposed age-related loss of brain reserve.

The Study of Anatomic Relationship Between the Müller Muscle and the Tarsus in Asian Upper Eyelid

This study was performed to clarify the detailed anatomic relationship between the insertion of Müller muscle and the tarsus in Asian upper eyelids. Eight upper eyelids of 4 formalin-fixed Asian cadavers (4 males; age range, 48-69 years; mean age, 60.2 years) were examined. Three perpendicular dissected sections with a 2-mm thickness were obtained from each eyelid. One section was obtained from the midline, and another 2 sections were obtained, each 3-mm from the lateral and medial ends of the tarsus, respectively. Samples were stained with hematoxylin-eosin, Masson trichrome, and antismooth muscle actin antibody and examined microscopically. Müller muscle did not insert directly in the tarsus. However, its muscle tissues were tapered to the superior margin of the tarsus, and the space between the Müller muscle and the tarsus was bridged by fibrous connective tissue strands. Meanwhile, according to a result that measured distance between the Müller muscle insertion and the tarsus, the insertion of Müller muscle was positioned closer in the tarsus at the midline section than at the lateral or medial sections. This study suggests that the Müller muscle is broadly distributed around the superior border of the tarsus as tapered, aggregated smooth muscle bundles without direct insertion on the superior border of the tarsus, despite a few limitation.

Connective tissue strands anchoring fat-body lobes in the silkworm, Bombyx mori

Connective tissue strands anchoring fat-body lobes in the silkworm, Bombyx mori

How to attach the limb to the body axis

While the question “How to make a limb” is extensively addressed in terms of pattern formation, morphogenesis, and genetic background, the ontophyletic scenario of attaching the limb to the axial skeleton via girdles has been paid much less attention. In a comparative study we have investigated pelvis morphogenesis and axio‐appendicular linkage in species from different vertebrate classes. Series of developmental stages from frog tadpoles1, chick embryos and mouse embryos2 were serially sectioned, and 3D‐reconstructed3. The 3D‐models were aligned to 4D‐visualizations of developmental dynamics and further analyzed.Our data reveal, that in all three species ‐ at the morphological level ‐ the pelvic element originates from a single anlage in close relation to the femur. Shape and orientation, however, differ already at initial stages and are followed by divergent subsequent morphogenesis. The timing and patterns of ossification are significantly different. In frog tadpoles a connective tissue strand serves a guiding function for attachment to the sacral vertebra1.These results demonstrate substantial differences in the establishment of the axio‐appendicular linkage among vertebrates and prompt for clarification of their genetic and epigenetic background.

Massive coats disease-like tumor after retinal detachment.

To describe two patients with peripheral Coats disease-like tumor reaction years after surgical repair for rhegmatogenous retinal detachment. Retrospective review of two clinical cases. Patient 1 presented with visual deterioration caused by a retinal angiomatous tumor and lipid exudates originating from telangiectatic vessels on the scleral buckle 8 years after vitrectomy and encircling band surgery for a giant retinal tear. In Patient 2, a vascularized retinal mass was detected during vitrectomy for a vitreous hemorrhage 24 years after scleral buckling procedures. Both patients were highly myopic and had no history of scleral perforation or angiomatous proliferation before surgery. They underwent vitrectomy and removal of the vascularized tumor. Histologic examination revealed wide lacunae filled with erythrocytes, connective tissue strands with inflammatory cells, and capillaries that showed thickened multilamellar basement membranes. Secondary Coats disease-like tumor reaction may occur as a late complication years after successful retinal detachment surgery and may be caused by a chronic ischemic and inflammatory stimulus induced by prominent buckling elements in highly myopic eyes.

A Guidance Channel Seeded With Autologous Schwann Cells for Repair of Cauda Equina Injury in a Primate Model

Background/Objective: To evaluate an implantable guidance channel (GC) seeded with autologous Schwann cells to promote regeneration of transected spinal nerve root axons in a primate model.Methods: Schwann cells were obtained from sural nerve segments of monkeys (Macaca fascicularis; cynomolgus). Cells were cultured, purified, and seeded into a PAN/PVC GC. Approximately 3 weeks later, monkeys underwent laminectomy and dural opening. Nerve roots of the L4 through L7 segments were identified visually. The threshold voltage needed to elicit hindlimb muscle electromyography (EMG) after stimulation of intact nerve roots was determined. Segments of 2 or 3 nerve roots (each ∼8-15 mm in length) were excised. The GC containing Schwann cells was implanted between the proximal and distal stumps of these nerve roots and attached to the stumps with suture. Follow-up evaluation was conducted on 3 animals, with survival times of 9 to 14 months.Results: Upon reexposure of the implant site, subdural nerve root adhesions were noted in all 3 animals. Several of the implanted GC had collapsed and were characterized by thin strands of connective tissue attached to either end. In contrast, 3 of the 8 implanted GC were intact and had white, glossy cables entering and exiting the conduits. Electrical stimulation of the tissue cable in each of these 3 cases led to low-threshold evoked EMG responses, suggesting that muscles had been reinnervated by axons regenerating through the repair site and into the distal nerve stump. During harvesting of the GC implant, sharp transection led to spontaneous EMG in the same 3 roots showing a low threshold to electrical stimulation, whereas no EMG was seen when harvesting nerve roots with high thresholds to elicit EMG. Histology confirmed large numbers of myelinated axons at the midpoint of 2 GC judged to have reinnervated target muscles.Conclusions: We found a modest rate of successful regeneration and muscle reinnervation after treatment of nerve root transection with a Schwann cell-seeded, implanted synthetic GC. Newer treatments, which include the use of absorbable polymers, neurotrophins, and antiscar agents, may further improve spinal nerve regeneration for repair of cauda equina injury.

How to attach the limb to the body axis

While the question “How to make a limb” is extensively addressed in terms of pattern formation, morphogenesis, and genetic background, the ontophyletic scenario of attaching the limb to the axial skeleton via girdles has been paid much less attention. In a comparative study we have investigated pelvis morphogenesis and axio‐appendicular linkage in species from different vertebrate classes. Series of developmental stages from frog tadpoles1, chick embryos and mouse embryos2 were serially sectioned, and 3D‐reconstructed3. The 3D‐models were aligned to 4D‐visualizations of developmental dynamics and further analyzed.Our data reveal, that in all three species ‐ at the morphological level ‐ the pelvic element originates from a single anlage in close relation to the femur. Shape and orientation, however, differ already at initial stages and are followed by divergent subsequent morphogenesis. The timing and patterns of ossification are significantly different. In frog tadpoles a connective tissue strand serves a guiding function for attachment to the sacral vertebra1.These results demonstrate substantial differences in the establishment of the axio‐appendicular linkage among vertebrates and prompt for clarification of their genetic and epigenetic background.