Abstract
The immune system can powerfully mobilize inflammatory cells to combat invading organisms, such as bacteria or viruses, but can also orchestrate the right balance of inflammatory components required to initiate tissue repair and regeneration following injury. Inflammatory responses have a finite initiation and to prevent ongoing host tissue damage, a finite resolution. However, there are instances in which such inflammation continues unabated, such as the nonhealing wound, chronic rejection of a transplanted organ or tissue, or the ongoing tissue destruction observed in autoimmune diseases. Recapitulating the body's own method of ending the inflammatory process has been the foundation of a number of strategies involving the regeneration of the immune system. These strategies can be divided by their cell of origin, hematopoietic cells, which are progenitors of all the cells of the immune system or nonhematopoietic stromal-type cells, which intimately interface with hematopoietic cells and provide regulation of the immune system. In hematopoietic cell–based strategies, there are two broad categories: (1) redesigning the entire immune system through partial or full replacement (mixed or full chimerism, respectively) and (2) selective component therapy aimed at reducing specific deleterious immune effects. Nonhematopoietic-based or stromal cell therapies can address both immune responses and facilitate regenerative responses directly through the production of matrix, growth factors, and targeted recruitment of proregenerative cell types. The manner in which hematopoietic and nonhematopoietic cell strategies are undertaken, the sources of cells used, preclinical efficacy studies, clinical outcomes, if known, and potential obstacles are discussed.