Cell therapy strategies for organ regeneration

The development of techniques to culture and differentiate adult and pluripotent stem cells into diverse cell types over the past decades has sparked an increasing interest in the use of cells for organ regeneration. Such therapies aim to replace lost or damaged cells with functional ones. This can be achieved either through tissue engraftment of therapeutic cells or via their paracrine effects on resident cells, thereby offering a potential cure for debilitating degenerative diseases. The development of regenerative cell therapies, however, is ultimately complex. Effective cell therapy requires the delivery and successful engraftment of therapeutic cells to the correct location or sufficient paracrine activity, while ensuring safety is key to gaining support from funders, caregivers, and patients. A wide variety of cell sources has been used for the development of regenerative cell therapies, ranging from mesenchymal stromal cells (MSC) that act to stimulate local progenitor cells through their secretome to tissue-specific cell types differentiated from adult or pluripotent stem cells and organoids that engraft in tissues. While cell administration to patients is challenging based on both practical and ethical perspectives, the development of techniques to preserve transplant organs ex situ on machine perfusion devices offers a unique opportunity for studying regenerative cell therapy for organ repair in a safe and controllable environment. The present review addresses the current progress of cell therapy for organ regeneration of the intestine, kidney, liver, lung, and heart and discusses the challenges and opportunities of this potentially curing therapeutic approach.