Creating a Pro-Regenerative Tissue Microenvironment: Local Control is the Key

Abstract

The potential of regenerative medicine to restore tissues and organs compromised or lost due to disease, injury or aging has captured the public imagination and attracted many multidisciplinary researchers to the field. However, despite significant promise, translation to the clinic has so far been modest. This slow progress might at least in part be due to the technical complexity of traditional cellbased approaches, which require in vitro manufacturing of large quantities of high-quality clinical grade cells for transplantation, ensuring targeted delivery and survival of these cells in vivo, as well as promoting functional morphogenesis of the new tissues and their integration with host tissues. The regulatory path for Food and Drug Administration (FDA) approval of such complex therapies could be arduous. While cell-based therapies remain an important goal for the future of regenerative medicine, an alternative class of therapies—referred to as autotherapies (Lumelsky et al., 2018)—that does not rely on exogenous cell transplantation, but instead attempts to pattern a pro-regenerative tissue microenvironment to optimize endogenous regeneration, might have a simplified regulatory path, and holds significant promise for achieving functional tissue regeneration in vivo. While the autotherapies idea is not new (Krzyszczyk et al., 2018; Liu and Segura, 2020; Fetz and Bowlin, 2021), it is particularly important and timely now. Many recent scientific and technical advances, including those in the basic biology of tissue regeneration, single-cell analyses, data science, and bioinformatics, as well as in material science and bioengineering, could propel the field forward and fulfill the therapeutic promise of this class of therapies.