Mesenchymal stem cells (MSCs) are appealing candidate for tissue regeneration because of their ability to differentiate into many cell types (1). However, the use of stem cells has several problems such as complicated safety and quality management, high cost and difficult cell handling (2). On the other hand, MSCs secrete various trophic factors such as cytokines and growth factors that may regenerate damaged tissues (3). Because of limited survival and differentiation of transplanted MSCs, it has been proposed that paracrine effect of MSC secretion is the principal mechanism for tissue regeneration (4).
Some studies investigated the effect of MSC conditioned medium (MSC-CM) on various kinds of diseases/conditions such as wound healing, cardiac and ischemic diseases (5). The therapeutic effects of MSC-CM are due to the panel of growth factors and cytokines present in it. These factors inhibit apoptosis and improve cell proliferation (6). Also, MSC-CM stimulates mobilization and homing of endogenous stem cell in to the local site of injury, without the necessity for cell transplantation (2).
Administration of MSC-CM has improved bone healing in the rat models (7). It has shown that MSC-CM has a high potential for bone healing, mediated by cytokines such as TGF-?1, IGF-1, VEGEF and BMP-1. These factors regulate osteogenesis process, angiogenesis, cell migration, osteoblast proliferation and differentiation (8).
Another application of MSC-CM is the neurological disorders. Some researchers have reported that MSC-CM enhances motor activity after spinal cord injury. They have concluded that MSC-CM reduces neuronal apoptosis and stimulates angiogenesis. These effects are attributed to some factors in MSC-CM such as NGF and BDNF (9).
Also, therapeutic effect of MSC-CM was evaluated in arthritis model. The results showed that MSC-CM application decreases cartilage destruction and suppresses immune responses by creating a balance between pro and anti- inflammatory cytokines (10). The use of MSC-CM has several advantages compared to the use of stem cells such as easily CM package and transportation (5).
In conclusion, the use of MSC-CM in regenerative medicine has opened a new window in treatment of many clinical disorders. This procedure can establish a novel technique in tissue regeneration without the need for stem cells application.