Brain organoids, consciousness, ethics and moral status.

Advances in the field of human stem cells are often a source of public and ethical controversy. Researchers must frequently balance diverse societal perspectives on questions of morality with the pursuit of medical therapeutics and innovation. Recent developments in brain organoids make this challenge even more acute. Brain organoids are a new class of brain surrogate generated from human pluripotent stem cells (hPSCs). They have gained traction as a model for studying the intricacies of the human brain by using advancements in stem cell biology to recapitulate aspects of the developing human brain in vitro. However, recent observation of neural oscillations spontaneously emerging from these organoids raises the question of whether brain organoids are or could become conscious. At the same time, brain organoids offer a potentially unique opportunity to scientifically understand consciousness. To address these issues, experimental biologists, philosophers, and ethicists united to discuss the possibility of consciousness in human brain organoids and the consequent ethical and moral implications.

Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury.

The goal of stem cell therapy for spinal cord injury (SCI) is to restore motor function without exacerbating pain. Induced pluripotent stem cells (iPSC) may be administered by autologous transplantation, avoiding immunologic challenges. Identifying strategies to optimize iPSC-derived neural progenitor cells (hiNPC) for cell transplantation is an important objective. Herein, we report a method that takes advantage of the growth factor-like and anti-inflammatory activities of the fibrinolysis protease, tissue plasminogen activator tPA, without effects on hemostasis. We demonstrate that conditioning hiNPC with enzymatically-inactive tissue-type plasminogen activator (EI-tPA), prior to grafting into a T3 lesion site in a clinically relevant severe SCI model, significantly improves motor outcomes. EI-tPA-primed hiNPC grafted into lesion sites survived, differentiated, acquired markers of motor neuron maturation, and extended ßIII-tubulin-positive axons several spinal segments below the lesion. Importantly, only SCI rats that received EI-tPA primed hiNPC demonstrated significantly improved motor function, without exacerbating pain. When hiNPC were treated with EI-tPA in culture, NMDA-R-dependent cell signaling was initiated, expression of genes associated with stemness (Nestin, Sox2) was regulated, and thrombin-induced cell death was prevented. EI-tPA emerges as a novel agent capable of improving the efficacy of stem cell therapy in SCI.