Soluble Factors of Amnion-Derived Cells in Treatment of Inflammatory and Fibrotic Pathologies

Abstract

Inflammation is a complex defense mechanism characterized by leukocyte migration from the vasculature into damaged tissues and subsequent deposition of extracellular matrix resulting in tissue repair. The inflammatory process is generally categorized into an acute, rapid response, and a persistent but slowly evolving chronic condition, which may progress into inflammatory diseases. An excessive deposition of extracellular matrix leads to overgrowth, hardening, and/or scarring of tissues, defined as fibrosis. The amnion has been used as biomaterial in medicine for over 100 years and has been proven valuable for the treatment of different pathological conditions including wound healing. In light of recent reports, this article will review the effects of the amnion and its cellular components within the inflammatory-fibrotic scenario and the factors described so far that could be involved in these immunomodulatory actions. As proof of principles, we will also discuss pre-clinical and clinical applications of the amnion where advantage has been taken of its anti-inflammatory and anti-fibrotic properties. It is conceivable that the local host environment in which the amnion is placed may have a profound role in influencing the production and function of soluble factors and the shift towards different steps in triggering healing. The healing effect depends on time, dosage, and location of cytokine/growth factor production by the amnion, together with the influence of the host microenvironment. Indeed, determining the specific cascade of events that may define the role of the amnion in a given clinical situation remains a challenge.

Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?

“…av-MSCs are also known to secrete a variety of immunomodulatory factors [13,37,[39][40][41][42]. The application of Cdm from av-MSCs reduced progression of lung fibrosis in a mouse model [43] and led to favorable clinical outcomes when treating tendon and ligament injuries in horses [44].…”

“…Its beneficial effects are assigned to its antiinflammatory, immunomodulatory, and scar-formation-reducing properties [12]. Even though the exact mechanisms are not known yet, secreted factors are suggested to play an important role [13].…”

Immunogenicity of Decidual Stromal Cells in an Epidermolysis Bullosa Patient and in Allogeneic Hematopoietic Stem Cell Transplantation Patients

“…The fetal membrane consists of three layers, of which the amnion and the chorion are of fetal origin and the decidua parietalis is of maternal origin. The inner AM contains both stromal and epithelial cells, both of which have been studied in experimental models of tissue repair [38]. These cells express HLA class-I molecules, but AMs show low immunogenicity in experimental xenotransplantation [39].…”

Therapeutic Effect of Human Amniotic Membrane–Derived Cells on Experimental Arthritis and Other Inflammatory Disorders

“…Interestingly, cells derived from either the epithelial or mesenchymal layers of human amniotic membrane-derived cells (HAMCs) impair lymphocyte activation, dendritic cell maturation, and inflammatory cytokine production in vitro (9)(10)(11)(12)(13). Moreover, treatment with total amniotic membrane, amniotic-derived cells, or their conditioned medium was found to be protective in different models of inflammatory fibrotic conditions (9,12,14,15). On these bases, the use of HAMCs in the treatment of autoimmune diseases becomes an attractive possibility still to be explored.…”