Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

Cell Therapy for Stroke: A Mechanistic Analysis.

Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts. In the present work, we review the major clinical trials of cell therapy for stroke and highlight a mechanistic shift between the earliest studies, which aimed to replace dead and damaged neurons, and later ones that focused on exploiting the various neuromodulatory effects afforded by stem cells. We discuss why both mechanisms are worth pursuing and emphasize the means through which cell replacement can still be achieved.

The LACE+ Index as a Predictor of 90-Day Supratentorial Tumor Surgery Outcomes.

BACKGROUND: The LACE+ (Length of stay, Acuity of admission, Charlson Comorbidity Index [CCI] score, and Emergency department [ED] visits in the past 6 mo) index risk-prediction tool has never been successfully tested in a neurosurgery population. OBJECTIVE: To assess the ability of LACE+ to predict adverse outcomes after supratentorial brain tumor surgery. METHODS: LACE+ scores were retrospectively calculated for all patients (n = 624) who underwent surgery for supratentorial tumors at the University of Pennsylvania Health System (2017-2019). Confounding variables were controlled with coarsened exact matching. The frequency of unplanned hospital readmission, ED visits, and death was compared for patients with different LACE+ score quartiles (Q1, Q2, Q3, and Q4). RESULTS: A total of 134 patients were matched between Q1 and Q4; 152 patients were matched between Q2 and Q4; and 192 patients were matched between Q3 and Q4. Patients with higher LACE+ scores were significantly more likely to be readmitted within 90 d (90D) of discharge for Q1 vs Q4 (21.88% vs 46.88%, P = .005) and Q2 vs Q4 (27.03% vs 55.41%, P = .001). Patients with larger LACE+ scores also had significantly increased risk of 90D ED visits for Q1 vs Q4 (13.33% vs 30.00%, P = .027) and Q2 vs Q4 (22.54% vs 39.44%, P = .039). LACE+ score also correlated with death within 90D of surgery for Q2 vs Q4 (2.63% vs 15.79%, P = .003) and with death at any point after surgery/during follow-up for Q1 vs Q4 (7.46% vs 28.36%, P = .002), Q2 vs Q4 (15.79% vs 31.58%, P = .011), and Q3 vs Q4 (18.75% vs 31.25%, P = .047). CONCLUSION: LACE+ may be suitable for characterizing risk of certain perioperative events in a patient population undergoing supratentorial brain tumor resection.