Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease

Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10106 Molday ION Rhodamine B-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action

Volumetric measurements of paranasal sinuses and examination of sinonasal communication in healthy Shetland ponies: anatomical and morphometric characteristics using computed tomography.

BACKGROUND: Despite clinical importance and frequent occurrence of sinus disease, little is known about the size of paranasal sinuses and their communication in ponies and small horses. To examine the shape and volume of the paranasal sinuses and evaluate the sinonasal communication, three-dimensional (3D) reconstructions of computed tomography (CT) datasets of 12 healthy adult Shetland ponies were performed and analysed. Linear measurements of head length and width were taken. Using semi-automatic segmentation, 3D-models of all sinus compartments were created. Volumetric measurement of the seven sinus compartments were conducted and statistical analysis was performed. Sinus volumes were compared between the left and right sinuses and the relation to age and head size was evaluated. RESULTS: Structure and shape of the paranasal sinus system in Shetland ponies was similar to that of large horses. All seven sinus compartments on each side of the head were identified (rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, middle conchal sinus, frontal sinus, sphenopalatine sinus). The existence of a bilateral cranial and a caudal system formed by a maxillary septum was visible in all 12 individuals. The volumetric sizes of the left and right sinuses did not differ significantly (p > 0.05). A positive correlation between the size of the paranasal sinuses and the head length was shown. A relation between sinus volumes and age could not be proved in adult ponies aged > six years. Communication between single sinus compartments was identified. Furthermore, communication with the nasal cavity over the nasomaxillary aperture (Apertura nasomaxillaris) and a common sinonasal channel (Canalis sinunasalis communis) as well as its splitting up into a rostral and a caudolateral channel could be seen. Examination of the sinonasal communication was challenging and only a descriptive evaluation was possible. CONCLUSIONS: Our findings concerning the size, shape and volumetric dimensions of Shetland pony CT images could help improve CT interpretation of abnormal clinical cases as well as aiding clinicians to develop and select appropriate instruments for medical inspection and treatments

In Vivo Magic Angle Magnetic Resonance Imaging for Cell Tracking in Equine Low-Field MRI.

The magic angle effect increases the MRI signal of healthy tendon tissue and could be used for more detailed evaluation of tendon structure. Furthermore, it could support the discrimination of hypointense artefacts induced by contrast agents such as superparamagnetic iron oxide used for cell tracking. However, magic angle MRI of the equine superficial digital flexor tendon has not been accomplished in vivo in standing low-field MRI so far. The aim of this in vivo study was to evaluate the practicability of this magic angle technique and its benefit for tracking superparamagnetic iron oxide-labelled multipotent mesenchymal stromal cells. Six horses with induced tendinopathy in their forelimb superficial digital flexor tendons were injected locally either with superparamagnetic iron oxide-labelled multipotent mesenchymal stromal cells or serum. MRI included standard and magic angle image series in T1- and T2∗-weighted sequences performed at regular intervals. Image analysis comprised blinded evaluation and quantitative assessment of signal-to-noise ratio. The magic angle technique enhanced the tendon signal-to-noise ratio (P < 0.001). Hypointense artefacts were observable in the cell-injected superficial digital flexor tendons over 24 weeks and artefact signal-to-noise ratio differed significantly from tendon signal-to-noise ratio in the magic angle images (P < 0.001). Magic angle imaging of the equine superficial digital flexor tendon is feasible in standing low-field MRI. The current data demonstrate that the technique improves discrimination of superparamagnetic iron oxide-induced artefacts from the surrounding tendon tissue.Peer Reviewe

An anatomical study of the dorsal and ventral nasal conchal bullae and middle nasal conchae in normal Shetland ponies: Computed tomographic anatomical and morphometric findings.

Equine paranasal sinuses are susceptible to inflammation. Insufficient drainage through the nasal passages and meatus may lead to the accumulation of inspissated purulent discharge. Particularly in ponies, these anatomical structures are suspected to be relatively small. To date, there are no reports considering the morphology of nasal conchal bullae in small horse breeds such as Shetland ponies. The aim of the present study was to evaluate the size of the conchal bullae and the medial nasal conchae of Shetland ponies and their relation to the skull dimension using computed tomography. Reconstructed images of healthy adult heads of Shetland ponies were used. Linear skull measurements as well as two cranial indices of the head dimensions were taken. Length, width and height of the dorsal and ventral conchal bullae and the medial nasal conchae were measured in relation to the skull and compared with the data of skulls of large breed horses. The anatomical proportions of pony heads were characterized by a smaller cranial index and a greater nasal index than those of large breed horses. Shetland ponies showed a longer cranial length compared with the nasal length. Heads are consistently smaller, and the relationship of the bullae to the head length was also smaller than those measured in large breed horses. A negative correlation between the head and bullae size was found. In conclusion, this study suggests that Shetland ponies have distinguishing proportions of the head. These findings are relevant for clinical examination and surgical treatment of equine sinus disease in those breeds

Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease.

Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10 × 10 6 Molday ION Rhodamine B™-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action

Effect of scan plane and arthrography on visibility and inter-observer agreement of the equine distal sesamoidean impar ligament on magnetic resonance images

In magnetic resonance imaging (MRI) examinations, moderate to severe changes of the distal sesamoidean impar ligament (DSIL) were found in horses with lameness localized to their feet. Histologic abnormalities were detected more commonly in lame horses. Because of its heterogeneity and small thickness, evaluation of the DSIL in MRI can be challenging. The aim of the study was to determine the optimal sequence and the ideal transverse perpendicular angle for visualization of the DSIL before and after arthrography of the distal interphalangeal joint (DIPJ). Twenty-five cadaver forelimbs were examined with low-field MRI. Sagittal, frontal, and three different angled transverse planes were obtained before and after arthrography of the DIPJ. All planes were acquired in T1w (weighted) Gradient Recall Echo (GRE), T2∗w GRE, T2w Fast Spin Echo (FSE), and Short Tau Inversion Recovery (STIR) FSE and visualization of the DSIL was scored by two observers. Visualization of the DSIL was best on sagittal T2w FSE and STIR FSE images. All transverse planes were inferior compared with sagittal sequences. After arthrography of the DIPJ, visualization of the DSIL origin improved in sagittal T2w FSE sequences, and agreement between observers increased for sagittal T2w FSE and STIR FSE images. Sagittal T2w FSE and STIR FSE images allowed good visualization of the DSIL in low-field MRI. Visualization of the DSIL did not improve for altered angled transverse sequences but increased with arthrography of the DIPJ. Subjective influence between different observers was found but decreased with DIPJ arthrography

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Volumetric measurements of paranasal sinuses and examination of sinonasal communication in healthy Shetland ponies: anatomical and morphometric characteristics using computed tomography

Background: Despite clinical importance and frequent occurrence of sinus disease, little is known about the size of paranasal sinuses and their communication in ponies and small horses. To examine the shape and volume of the paranasal sinuses and evaluate the sinonasal communication, three-dimensional (3D) reconstructions of computed tomography (CT) datasets of 12 healthy adult Shetland ponies were performed and analysed. Linear measurements of head length and width were taken. Using semi-automatic segmentation, 3D-models of all sinus compartments were created. Volumetric measurement of the seven sinus compartments were conducted and statistical analysis was performed. Sinus volumes were compared between the left and right sinuses and the relation to age and head size was evaluated. Results: Structure and shape of the paranasal sinus system in Shetland ponies was similar to that of large horses. All seven sinus compartments on each side of the head were identified (rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, middle conchal sinus, frontal sinus, sphenopalatine sinus). The existence of a bilateral cranial and a caudal system formed by a maxillary septum was visible in all 12 individuals. The volumetric sizes of the left and right sinuses did not differ significantly (p > 0.05). A positive correlation between the size of the paranasal sinuses and the head length was shown. A relation between sinus volumes and age could not be proved in adult ponies aged > six years. Communication between single sinus compartments was identified. Furthermore, communication with the nasal cavity over the nasomaxillary aperture (Apertura nasomaxillaris) and a common sinonasal channel (Canalis sinunasalis communis) as well as its splitting up into a rostral and a caudolateral channel could be seen. Examination of the sinonasal communication was challenging and only a descriptive evaluation was possible. Conclusions: Our findings concerning the size, shape and volumetric dimensions of Shetland pony CT images could help improve CT interpretation of abnormal clinical cases as well as aiding clinicians to develop and select appropriate instruments for medical inspection and treatments

Characterization of Equine Chronic Tendon Lesions in Low- and High-Field Magnetic Resonance Imaging

In equine medicine, experience regarding MRI of chronic tendon lesions is limited, and evidence on the suitability of different sequences in 3 T high-field MRI is scarce. Therefore, macroscopically healthy and altered tendons were examined by histology and in 0.27 T low- and 3 T high-field MRI, focusing on T1-weighted (T1w) sequences to visualize chronic lesions. In high-field MRI, tendons were positioned parallel (horizontal) and perpendicular (vertical) to the magnetic field, acknowledging the possible impact of the magic angle effect. The images were evaluated qualitatively and signal intensities were measured for quantitative analysis. Qualitative evaluation was consistent with the quantitative results, yet there were differences in lesion detection between the sequences. The low-field T1w GRE sequence and high-field T1w FLASH sequence with vertically positioned tendons displayed all tendon lesions. However, the horizontally scanned high-field T1w SE sequence failed to detect chronic tendon lesions. The agreement regarding tendon signal intensities was higher between high-field sequences scanned in the same orientation (horizontal or vertical) than between the same types of sequence (SE or FLASH), demonstrating the impact of tendon positioning. Vertical scanning was superior for diagnosis of the tendon lesions, suggesting that the magic angle effect plays a major role in detecting chronic tendon disease

Isomorphism and Decoupling: Processes of External and Internal Legitimation in Southeast Asia

Wie können widersprüchliche Modernisierungsprozesse der Staaten Südostasiens analysiert werden Auf der einen Seite zeigen die Staaten Kennzeichen moderner Staaten, während auf der anderen Seite traditionelle Formen wie Patronage, Cronyism usw. ein Merkmal der Staatsverwaltungen sind. Gleichzeitig sind die politischen und Verwaltungssysteme erstaunlich stabil und dazu in der Lage, einen Rahmen für rapide wirtschaftliche Entwicklung zu bilden. Im Artikel verwenden wir eine neo-instutionalistische Perspektive, vor allem Überlegungen zu ‘decoupling‘ von Organisations- und Handlungsstruktur, um so die Diskrepanzen zwischen modernen Formen der Staaten mit ‘asiatischen‘ Inhalten zu erfassen. Der neo-institutionalistische Ansatz wird mit dem Konzept der ‘multiple modernities‘ und ‘umstrittener Institutionalisierung‘ verbunden. So lassen sich die parellelen Prozesse von Universalisierungen, die sich aus Interdependenzen von Organisationen in einem ‘organisational field‘ ergeben, mit Prozessen der Partikularisierung verbinden, durch die sich vielfältige Handlungsmöglichkeiten innerhalb der Staatsorganisation ergeben. Thailand und Myanmar wurden als Beispiele gewählt, da Thailand immer eine Strategie der internationalen Integration verfolgte, gegenüber dem auf Isolation bedachten Verhalten Myanmars. Summary How is it possible to analyse the seemingly contradictory modernization processes in Southeast Asian states On the one hand, these states feature the universal characteristics of modern states, while on the other, seemingly traditional patterns such as patronage, cronyism, etc. are an integral part of their administrations. Furthermore, the states and bureaucracies are fairly stable and able to provide a framework for rapid economic development. This article combines a neo-institutionalist perspective that allows us to ‘decouple’ organizational structures from action structures, and thus take into account the discrepancy between the modern form and supposedly ‘Asian’ content of the states. It also considers the facts in the light of concepts such as ‘multiple modernities’ and ‘contested institutionalism’. Thus, different modernization processes that lead to universalism are present, resulting from the interdependency of organizations within a global organizational field, as well as particularism which enables diversity in action. Thailand and Myanmar are taken as case studies, because Thailand has always followed a strategy of international integration, in contrast to isolationist Myanmar