Direct reprogramming of amniotic cells into endothelial cells

Abstract

Organ regeneration promises unlimited access to replacement tissues. The current paradigm of organ regeneration requires transplantation of adult tissue-restricted stem and progenitor cells to repair the damaged organ. However, healing injured organs often leads to fibrosis with little recovery of function. An alternative approach is to harness the regenerative activity of microvascular endothelial cells (ECs) to support endogenous organ repair. Recent work demonstrates that organ regeneration can be directed by paracrine mediators, called Angiocrine Factors, elaborated by tissue-specific ECs to support stem and progenitor cells to directly induce organ regeneration without maladaptive fibrosis. Yet, the regenerative function and the repertoire of angiocrine factors elaborated by ECs depend upon the organ from which they originate. New technologies have emerged to transcriptionally reprogram amniotic fluid cells (ACs) into generic unspecified ECs that acquire tissue-specific function promises a ready source of transplantable ECs to be used for organ regeneration. Generic AC-derived ECs can be induced to acquire organ-specific functions by a process of in vivo education wherein extravascular cues trigger transcriptional programs within engrafted ECs enabling them to acquire tissue-specific functions and to deploy angiocrine growth factors that drive organ repair without aberrant pro-fibrotic remodeling. Identifying tissue-specific transcription factors regulating tissue specification of EC is at the frontier of this new approach for organ regeneration. The chapter is expected to overturn the scientific conceptualization of a monofunctional, inert, microvasculature by revealing a dynamic, tissue-specified role for ECs in organ repair that will enable therapeutic use of educated, tissue-specified ECs that home to their native injured organs and supply tissue-specific angiocrine signals to orchestrate organ regeneration.