Jingru Che

All Publications

• Modulating the platelet-mediated innate foreign body response to affect in situ vascular tissue engineering outcomes. NPJ Regenerative medicine Turner, M. E., Che, J., Leland, J. T., Villarreal, D. J., Rajesh, S., Suravarapu, S., Hor, K. N., Wiet, M. G., Kerlin, B. A., Yi, T., Best, C. A., Reinhardt, J. W., Breuer, C. K. 2025; 10 (1): 34

  Abstract

  The success of implanted tissue-engineered vascular grafts (TEVGs) relies on the coordinated inflammation and wound healing processes that simultaneously degrade the scaffold and guide the formation of a neovessel. Dysregulated responses can lead to aberrant remodeling (e.g., stenosis), impacting the long-term outcome and functionality of the TEVG. We developed a TEVG that, despite demonstrating growth capacity in the clinic, exhibited an unexpectedly high incidence of stenosis, or narrowing of the graft lumen. This study identified platelet-mediated immune signaling via the lysosomal trafficking regulator (Lyst) as a key driver of stenosis. Lyst mutations significantly impaired platelet dense granule exocytosis yet preserved alpha granule secretion and adhesion to the biomaterial. Uncontrolled platelet aggregation, potentiated by dense granule signaling, results in the formation of a mural thrombus that remodels into occlusive neotissue. Importantly, inhibiting sustained platelet aggregation using the P2Y12 antagonist, prasugrel, is a successful strategy for optimizing neotissue formation and improving overall TEVG performance.

  View details for DOI 10.1038/s41536-025-00419-w

  View details for PubMedID 40691447

  View details for PubMedCentralID PMC12279924

• Dynamic Narrowing of the Diaphragmatic Vena Cava in Ovis aries. Anatomia, histologia, embryologia Schwartzman, W. E., Turner, M. E., Spiess, J. L., Jimenez, M., Watanabe, T., Hama, R., Che, J., Kelly, G. L., Yimit, A., Baker, P. B., Arsuaga-Zorrilla, C., Kelly, J., Breuer, C. K., Best, C. A., Reinhardt, J. W. 2024; 53 (6): e13114

  Abstract

  Dorset sheep (Ovis aries) are common models in translational cardiovascular research due to physiologic and anatomic similarities to humans. While employing ovine subjects to study single-ventricle physiology, we repeatedly observed position-based changes in central venous pressure (CVP) which could not be explained by hydrostatic (gravitational) effects. Inferior vena cava (IVC) narrowing or compression has been demonstrated in numerous species, and we hypothesised that this phenomenon might explain our observations in O. aries. This study aimed to characterise position-dependent morphology of the IVC in O. aries using catheter-based hemodynamic and dimensional measurements, three-dimensional MRI reconstruction and histological analysis. Baseline measurements revealed a significant reduction in IVC dimensions at the level of the diaphragm (dVC) compared to the abdominal vena cava (aVC) and thoracic vena cava (tVC). We also observed a transdiaphragmatic pressure gradient along the IVC, with higher pressures in the aVC compared to the tVC. We found that variation of position and fluid status altered IVC haemodynamics. Histological data showed variable muscularity along the length of the IVC, with greater smooth muscle content in the aVC than the tVC. These findings will improve understanding of baseline ovine physiology, help refine experimental protocols and facilitate the translation of findings to the clinic.

  View details for DOI 10.1111/ahe.13114

  View details for PubMedID 39403062

  View details for PubMedCentralID PMC11500010

• The lysosomal trafficking regulator "LYST": an 80-year traffic jam. Frontiers in immunology Turner, M. E., Che, J., Mirhaidari, G. J., Kennedy, C. C., Blum, K. M., Rajesh, S., Zbinden, J. C., Breuer, C. K., Best, C. A., Barker, J. C. 2024; 15: 1404846

  Abstract

  Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.

  View details for DOI 10.3389/fimmu.2024.1404846

  View details for PubMedID 38774881

  View details for PubMedCentralID PMC11106369

• Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model. Comparative medicine Schwartzman, W. E., Che, J., Naguib, M. A., Palillo, J., Jimenez, M., Turner, M. E., Yates, A. R., Arsuaga-Zorrilla, C., Breuer, C., Kelly, J. 2024; 74 (2): 70-80

  Abstract

  Whole blood analysis can evaluate numerous parameters, including pH, pCO₂, pO₂, HCO₃ - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO₂, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

  View details for DOI 10.30802/AALAS-CM-24-000008

  View details for PubMedID 38508687

  View details for PubMedCentralID PMC11078283

• αCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform. Biotechnology and bioengineering Che, J., DePalma, T. J., Sivakumar, H., Mezache, L. S., Tallman, M. M., Venere, M., Swindle-Reilly, K., Veeraraghavan, R., Skardal, A. 2023; 120 (4): 1108-1119

  Abstract

  Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.

  View details for DOI 10.1002/bit.28313

  View details for PubMedID 36544242