Improved approach for chondrogenic differentiation of human induced pluripotent stem cells

Human induced pluripotent stem cells (hiPSCs) have demonstrated great potential for hyaline cartilage regeneration. However, current approaches for chondrogenic differentiation of hiPSCs are complicated and inefficient primarily due to intermediate embryoid body formation, which is required to generate endodermal, ectodermal, and mesodermal cell lineages. We report a new, straightforward and highly efficient approach for chondrogenic differentiation of hiPSCs, which avoids embryoid body formation. We differentiated hiPSCs directly into mesenchymal stem /stromal cells (MSC) and chondrocytes. hiPSC-MSC-derived chondrocytes showed significantly increased Col2A1, GAG, and SOX9 gene expression compared to hiPSC-MSCs. Following transplantation of hiPSC-MSC and hiPSC-MSC-derived chondrocytes into osteochondral defects of arthritic joints of athymic rats, magnetic resonance imaging studies showed gradual engraftment, and histological correlations demonstrated hyaline cartilage matrix production. Results present an efficient and clinically translatable approach for cartilage tissue regeneration via patient-derived hiPSCs, which could improve cartilage regeneration outcomes in arthritic joints

Radiological-pathological correlation of pleomorphic liposarcoma of the anterior mediastinum in a 17-year-old girl

Liposarcoma is a soft-tissue sarcoma typically seen in adults. It is extremely rare in children. It most often occurs in the extremities or in the retroperitoneum. We present a very rare case of an anterior mediastinal liposarcoma of the pleomorphic subtype in a 17-year-old girl, along with radiological and pathological correlation. The location, patient age and histological subtype are exceedingly uncommon for this tumor

Accelerated stem cell labeling with ferucarbotran and protamine

To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1–24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent

MR imaging of therapy-induced changes of bone marrow

MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment

Animal Models and Their Role in Imaging-Assisted Co-Clinical Trials

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients\u27 tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant optimization is quantitative imaging. The National Cancer Institute has organized a Co-Clinical Imaging Resource Program (CIRP) network to establish best practices for co-clinical imaging and to optimize translational quantitative imaging methodologies. This overview describes the ten co-clinical trials of investigators from eleven institutions who are currently supported by the CIRP initiative and are members of the Animal Models and Co-clinical Trials (AMCT) Working Group. Each team describes their corresponding clinical trial, type of cancer targeted, rationale for choice of animal models, therapy, and imaging modalities. The strengths and weaknesses of the co-clinical trial design and the challenges encountered are considered. The rich research resources generated by the members of the AMCT Working Group will benefit the broad research community and improve the quality and translational impact of imaging in co-clinical trials

Routine MRI findings of the asymptomatic foot in diabetic patients with unilateral Charcot foot

<p>Abstract</p> <p>Background</p> <p>Imaging studies of bones in patients with sensory deficits are scarce.</p> <p>Aim</p> <p>To investigate bone MR images of the lower limb in diabetic patients with severe sensory polyneuropathy, and in control subjects without sensory deficits.</p> <p>Methods</p> <p>Routine T1 weighted and T2-fat-suppressed-STIR-sequences without contrast media were performed of the asymptomatic foot in 10 diabetic patients with polyneuropathy and unilateral inactive Charcot foot, and in 10 matched and 10 younger, non-obese unmatched control subjects. Simultaneously, a Gadolinium containing phantom was also assessed for reference. T1 weighted signal intensity (SI) was recorded at representative regions of interest at the peritendineal soft tissue, the tibia, the calcaneus, and at the phantom. Any abnormal skeletal morphology was also recorded.</p> <p>Results</p> <p>Mean SI at the soft tissue, the calcaneus, and the tibia, respectively, was 105%, 105% and 84% of that at the phantom in the matched and unmatched control subjects, compared to 102% (soft tissue), 112% (calcaneus) and 64% (tibia) in the patients; differences of tibia vs. calcaneus or soft tissue were highly significant (p < 0.005). SI at the tibia was lower in the patients than in control subjects (p < 0.05). Occult traumatic skeletal lesions were found in 8 of the 10 asymptomatic diabetic feet (none in the control feet).</p> <p>Conclusion</p> <p>MR imaging did not reveal grossly abnormal bone marrow signalling in the limbs with severe sensory polyneuropathy, but occult sequelae of previous traumatic injuries.</p

Optical imaging of the peri-tumoral inflammatory response in breast cancer

<p>Abstract</p> <p>Purpose</p> <p>Peri-tumoral inflammation is a common tumor response that plays a central role in tumor invasion and metastasis, and inflammatory cell recruitment is essential to this process. The purpose of this study was to determine whether injected fluorescently-labeled monocytes accumulate within murine breast tumors and are visible with optical imaging.</p> <p>Materials and methods</p> <p>Murine monocytes were labeled with the fluorescent dye DiD and subsequently injected intravenously into 6 transgenic MMTV-PymT tumor-bearing mice and 6 FVB/n control mice without tumors. Optical imaging (OI) was performed before and after cell injection. Ratios of post-injection to pre-injection fluorescent signal intensity of the tumors (MMTV-PymT mice) and mammary tissue (FVB/n controls) were calculated and statistically compared.</p> <p>Results</p> <p>MMTV-PymT breast tumors had an average post/pre signal intensity ratio of 1.8+/- 0.2 (range 1.1-2.7). Control mammary tissue had an average post/pre signal intensity ratio of 1.1 +/- 0.1 (range, 0.4 to 1.4). The p-value for the difference between the ratios was less than 0.05. Confocal fluorescence microscopy confirmed the presence of DiD-labeled cells within the breast tumors.</p> <p>Conclusion</p> <p>Murine monocytes accumulate at the site of breast cancer development in this transgenic model, providing evidence that peri-tumoral inflammatory cell recruitment can be evaluated non-invasively using optical imaging.</p

Rat model of metastatic breast cancer monitored by MRI at 3 tesla and bioluminescence imaging with histological correlation

<p>Abstract</p> <p>Background</p> <p>Establishing a large rodent model of brain metastasis that can be monitored using clinically relevant magnetic resonance imaging (MRI) techniques is challenging. Non-invasive imaging of brain metastasis in mice usually requires high field strength MR units and long imaging acquisition times. Using the brain seeking MDA-MB-231BR transfected with luciferase gene, a metastatic breast cancer brain tumor model was investigated in the nude rat. Serial MRI and bioluminescence imaging (BLI) was performed and findings were correlated with histology. Results demonstrated the utility of multimodality imaging in identifying unexpected sights of metastasis and monitoring the progression of disease in the nude rat.</p> <p>Methods</p> <p>Brain seeking breast cancer cells MDA-MB-231BR transfected with firefly luciferase (231BRL) were labeled with ferumoxides-protamine sulfate (FEPro) and 1-3 × 10⁶cells were intracardiac (IC) injected. MRI and BLI were performed up to 4 weeks to monitor the early breast cancer cell infiltration into the brain and formation of metastases. Rats were euthanized at different time points and the imaging findings were correlated with histological analysis to validate the presence of metastases in tissues.</p> <p>Results</p> <p>Early metastasis of the FEPro labeled 231BRL were demonstrated onT2*-weighted MRI and BLI within 1 week post IC injection of cells. Micro-metastatic tumors were detected in the brain on T2-weighted MRI as early as 2 weeks post-injection in greater than 85% of rats. Unexpected skeletal metastases from the 231BRL cells were demonstrated and validated by multimodal imaging. Brain metastases were clearly visible on T2 weighted MRI by 3-4 weeks post infusion of 231BRL cells, however BLI did not demonstrate photon flux activity originating from the brain in all animals due to scattering of the photons from tumors.</p> <p>Conclusion</p> <p>A model of metastatic breast cancer in the nude rat was successfully developed and evaluated using multimodal imaging including MRI and BLI providing the ability to study the temporal and spatial distribution of metastases in the brain and skeleton.</p