Microfluidic-Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease.

The knowledge of the blood microvasculature and its functional role in health and disease has grown significantly attributable to decades of research and numerous advances in cell biology and tissue engineering; however, the lymphatics (the secondary vascular system) has not garnered similar attention, in part due to a lack of relevant in vitro models that mimic its pathophysiological functions. Here, a microfluidic-based approach is adopted to achieve precise control over the biological transport of growth factors and interstitial flow that drive the in vivo growth of lymphatic capillaries (lymphangiogenesis). The engineered on-chip lymphatics with in vivo-like morphology exhibit tissue-scale functionality with drainage rates of interstitial proteins and molecules comparable to in vivo standards. Computational and scaling analyses of the underlying transport phenomena elucidate the critical role of the three-dimensional geometry and lymphatic endothelium in recapitulating physiological drainage. Finally, the engineered on-chip lymphatics enabled studies of lymphatic-immune interactions that revealed inflammation-driven responses by the lymphatics to recruit immune cells via chemotactic signals similar to in vivo, pathological events. This on-chip lymphatics platform permits the interrogation of various lymphatic biological functions, as well as screening of lymphatic-based therapies such as interstitial absorption of protein therapeutics and lymphatic immunomodulation for cancer therapy.

Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples.

Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and therefore a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour with a precision of 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. Applying this approach to human lymphocytes, we discovered that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we found that the ex vivo density response of primary tumor cells to drug treatment can predict in vivo tumor growth response. Our method reveals unexpected behavior in molecular crowding during cell state transitions and suggests density as a new biomarker for functional precision medicine.

Can preoperative magnetic resonance arthrography accurately predict intraoperative hip labral thickness?

OBJECTIVE: There is limited literature investigating the reliability of magnetic resonance-based assessments of labral size. The goal of this study was to validate the reliability of magnetic resonance arthrography-based labral size measurements with intra-operative arthroscopic measurements. METHODS: Patients undergoing hip arthroscopy for femoroacetabular impingement and labral tears were prospectively enrolled. Preoperative magnetic resonance arthrograms were used to determine labral size at the anterior-superior portion (zone 2), mid-superior portion (zone 3), and posterior-superior portion (zone 4). Intra-operative labral widths were measured at the same anatomical zones of the acetabulum using an arthroscopic probe. Mean labral size was determined for each location and a Pearson correlation was used to determine the correlation between imaging-based measurements and intra-operative measurements. RESULTS: 117 patients were enrolled with 70% being female, an average age of 39.1 ± 13.3, and an average body mass index was 26.5 ± 5.4. The average labral sizes based on intraoperative measurements were 6.85 mm in zone 2, 7.45 mm in zone 3, and 7.29 mm in zone 4. The average labral sizes based on MRA were 6.95 mm in zone 2, 7.24 mm in zone 3, and 6.71 mm in zone 4. There was a poor correlation between MRA and intraoperative measurements in zones 2 and 3 (zone 2: R = 0.171, p = 0.065; zone 3: R = 0.335, p = 0.00022) and no correlation in zone 4 (R = -0.22, p = 0.82). CONCLUSION: This study demonstrates a poor correlation in labral measurements between magnetic resonance arthrogram imaging and intraoperative measurements, suggesting that this imaging modality may be insufficient in providing accurate measurements of labral size.