The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

BACKGROUND There is recent support for long‐term adverse effects of donor‐recipient sex‐mismatched red blood cell (RBC) transfusion, but short‐term impact is unknown. A retrospective exploratory analysis was performed using data from a research database. METHODS Adults admitted to hospitals in one Canadian center who received RBCs (2008–2014 [3 sites]; 2012–2014 [1 site]) were eligible. Patient data were extracted from a research database and donor data from the blood supplier. Cox regression models were used, with control of risk and confounding variables as covariates or using stratification. Exposure was defined by mutually exclusive categories. The outcome was in‐hospital mortality. RESULTS A total of 25,219 adults received 97,886 RBCs. Diagnoses included cardiovascular (28.8%), neoplastic (15.6%), traumatic (15.4%), or gastrointestinal (10.5%); 56.3% of transfused RBCs were male donors, and median donor age was 45 years (interquartile range, 30–54). Female patients exposed to male RBCs experienced a higher risk of in‐hospital death (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.02–1.69; p = 0.038) compared to exclusive female RBC exposure. Exposure to RBCs from donors aged 45 years or younger was associated with a higher in‐hospital death (HR, 1.21; 95% CI, 1.02–1.44; p = 0.026) compared to exclusive RBC exposure to donors older than 45 years. Donor‐recipient sex‐mismatched RBC exposure (vs. exclusively sex‐matched) and RBC exposure from donors aged 45 years or younger (vs. exclusively RBCs from donors >45) were associated with increased mortality: sex‐mismatched (HR, 1.23; (95% CI, 1.04–1.45; p = 0.017); donors aged 45 years or younger (HR, 1.21; (95% CI, 1.02–1.43; p = 0.031). CONCLUSION Donor‐recipient sex‐matched RBC transfusions and transfusions from older donors may benefit patients.

Propagation of intracellular ice between cells significantly increases the prevalence of intracellular ice in confluent monolayers and tissues. It has been proposed that gap junctions facilitate ice propagation between cells. This study develops an equation for capillary freezing-point depression to determine the effect of temperature on the equilibrium radius of an ice crystal sufficiently small to grow through gap junctions. Convection cryomicroscopy and video image analysis were used to examine the incidence and pattern of intracellular ice formation (IIF) in the confluent monolayers of cell lines that do (MDCK) and do not (V-79W) form gap junctions. The effect of gap junctions on intracellular ice propagation was strongly temperature-dependent. For cells with gap junctions, IIF occurred in a directed wave-like pattern in 100% of the cells below -3 degrees C. At temperatures above -3 degrees C, there was a marked drop in the incidence of IIF, with isolated individual cells initially freezing randomly throughout the sample. This random pattern of IIF was also observed in the V-79W monolayers and in MDCK monolayers treated to prevent gap junction formation. The significant change in the low temperature behavior of confluent MDCK monolayers at -3 degrees C is likely the result of the inhibition of gap junction-facilitated ice propagation, and supports the theory that gap junctions facilitate ice nucleation between cells.

Stored red blood cells (RBCs) are needed for life-saving blood transfusions, but they undergo continuous degradation. RBC storage lesions are often assessed by microscopic examination or biochemical and biophysical assays, which are complex, time-consuming, and destructive to fragile cells. Here we demonstrate the use of label-free imaging flow cytometry and deep learning to characterize RBC lesions. Using brightfield images, a trained neural network achieved 76.7% agreement with experts in classifying seven clinically relevant RBC morphologies associated with storage lesions, comparable to 82.5% agreement between different experts. Given that human observation and classification may not optimally discern RBC quality, we went further and eliminated subjective human annotation in the training step by training a weakly supervised neural network using only storage duration times. The feature space extracted by this network revealed a chronological progression of morphological changes that better predicted blood quality, as measured by physiological hemolytic assay readouts, than the conventional expert-assessed morphology classification system. With further training and clinical testing across multiple sites, protocols, and instruments, deep learning and label-free imaging flow cytometry might be used to routinely and objectively assess RBC storage lesions. This would automate a complex protocol, minimize laboratory sample handling and preparation, and reduce the impact of procedural errors and discrepancies between facilities and blood donors. The chronology-based machine-learning approach may also improve upon humans’ assessment of morphological changes in other biomedically important progressions, such as differentiation and metastasis.