Role of stem/progenitor cells in reparative disorders

Tissue repair post-injury or during disease culminates in either complete restoration of tissue integrity, defined here as regeneration, or in a process that leads to the generation of stromal structures that replace functional tissue. These structures, while vital in ensuring tissue continuity, do not support, and in some instances even interfere with, tissue or organ function. The establishment of these stromal scars is referred herein as “repair”, and conditions in which they become predominant are called “reparative disorders”. This term encompasses diseases or symptoms exhibited during the repair process of damaged tissues that have been described in the literature since the early nineteenth century, including adipocyte accumulation (fatty degeneration), ectopic bone formation and fibrous tissue deposition [1-3]. In the context of mammalian biology, tissue regeneration is an essential process for restoring structure and function of traumatized organs. Regeneration of tissues is typically accompanied by acute or chronic inflammation caused by the disease or trauma, and involves the coordinated interaction among multiple cell types, including tissue specific stem/ progenitor cells (TSCs), mesenchymal stromal cells (MSCs) and immune cells. Many of the same cell types involved in regeneration also contribute to repair, suggesting that aberrant environmental cues and alterations of the signaling networks between these cells are central to the establishment of reparative disorders [4].Several sources have been proposed for the progenitors involved in reparative disorders, including local sources, such as the damaged tissues themselves, and systemic sources, such as the bone marrow [5]. Locally, both tissue specific stem cells and ubiquitous mesenchymal and endothelial progenitors have been implicated in the development of the cellular effectors of repair: fibrotic matrix producing cells, adipocytes and osteocytes. Systemically, a role has been proposed for bone marro