Selected Grantee Publications
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- Preservation
- Spectrometry
Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy
Racine et al., Journal of Immunology. 2024.
Myocarditis has emerged as a relatively rare but often lethal autoimmune complication of checkpoint inhibitor (ICI) cancer therapy, and significant mortality is associated with this phenomenon. Investigators developed a new mouse model system that spontaneously develops myocarditis. These mice are highly susceptible to myocarditis and acute heart failure following anti-PD-1 ICI-induced treatment. Additionally, the treatment accelerates skeletal muscle myositis. The team performed characterization of cardiac and skeletal muscle T cells using histology, flow cytometry, adoptive transfers, and RNA sequencing analyses. This study sheds light on underlying immunological mechanisms in ICI myocarditis and provides the basis for further detailed analyses of diagnostic and therapeutic strategies. Supported by ORIP (U54OD020351, U54OD030187), NCI, NIA, NIDDK, and NIGMS.
Conduction-Dominated Cryomesh for Organism Vitrification
Guo et al., Advanced Science. 2024.
https://pubmed.ncbi.nlm.nih.gov/38018294/
Vitrification-based cryopreservation via cryomesh is a promising approach for maintaining biodiversity, health care, and sustainable food production via long-term preservation of biological systems. Here, researchers conducted a series of experiments aimed at optimizing the cooling and rewarming rates of cryomesh to increase the viability of various cryopreserved biosystems. They found that vitrification was significantly improved by increasing thermal conductivity, reducing mesh wire diameter and pore size, and minimizing the nitrogen vapor barrier of the conduction-dominated cryomesh. Cooling rates increased twofold to tenfold in a variety of biosystems. The conduction-dominated cryomesh improved the cryopreservation outcomes of coral larvae, Drosophila embryos, and zebrafish embryos by vitrification. These findings suggest that the conduction-dominated cryomesh can improve vitrification in such biosystems for biorepositories, agriculture and aquaculture, and research. Supported by ORIP (R24OD028444, R21OD028758, R24OD034063, R21OD028214), NIDDK, and NIGMS.
Orthotopic Transplantation of the Full-Length Porcine Intestine After Normothermic Machine Perfusion
Abraham et al., Transplantation Direct. 2022.
https://www.doi.org/10.1097/TXD.0000000000001390
Successful intestinal transplantation currently is hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation could expand transplantable graft numbers and enhance post-transplant outcomes. Superior transplant outcomes recently have been demonstrated in clinical trials using machine perfusion to preserve the liver. The investigators report the development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model. Supported by ORIP (K01OD019911), NIAID, and NIDDK.
Rapid Joule Heating Improves Vitrification Based Cryopreservation
Zhan et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-33546-9
Cryopreservation by vitrification is an effective approach for long-term preservation of biosystems, but effective vitrification often requires high concentrations of cryoprotective agent (CPA), which can be toxic. The investigators described a joule heating–based platform technology for rapid rewarming of biosystems, which allows the use of low concentrations of CPA. They demonstrated the success of this platform in cryopreservation of three model systems: adherent cells, Drosophila melanogaster embryos, and rat kidney slices with low CPA concentrations. This work provides a general solution to cryopreserve a broad spectrum of cells, tissues, organs, and organisms. Supported by ORIP (R21OD028758), NIDDK, NHLBI, and NIGMS.