Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrine activities on exogenous MSCs: Implications for paracrine activities in bone regeneration

Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration

“…Stem cells secrete a broad repertoire of trophic and immunomodulatory factors [42]. Recent preclinical studies have reported that secretomes from MSC have the potential for treating some intractable diseases as acute myocardial infarction [16], fulminant hepatic failure [43], renal failure [44], [45], ischemic stroke [46], experimental autoimmune encephalomyelitis [47] and hypoxic brain injury [48] and for the repair of soft tissues [49]. Also, has been reported that MSC-CM has a very high potential for bone regeneration, mediated by the cooperative effects of cytokines such as IGF-1, TGF-ß1 [50], [51], VEGF, angiogenin [50], HGF (Hepatocyte growth factor) [51], BMP-1 [52], IL-6, IL-3, MCP-1 (Monocyte Chemoattractant Protein-1) and MCP-3 (Monocyte Chemoattractant Protein-3) [41].…”

“…These findings are consistent with results obtained by Horie M, et al, who found that human MSC promote regeneration of articular disk in a rat model although they not persist over the injury site [14], raising some questions about the mechanisms by which MSC contribute to tissue repair after transplantation. While the answers are not completely known, accumulating evidence suggest that the therapeutic potential of MSC can be attributed not only to differentiation and integration into the injured tissue [49] but mainly to the ability to secrete soluble factors that functionally modulate the microenvironment of the host tissue in order to facilitate the endogenous process of regeneration [9], [49]. This hypothesis is supported by in vitro and in vivo studies showing that many cell types respond to paracrine signaling from MSC, regulating a large number of cellular responses, such as survival, proliferation, migration, gene expression [11], and increasing the tissue repair process in response to the application of MSC conditioned media [15], [16].…”

Advancing the cellular and molecular therapy for intervertebral disc disease

“…Moreover, Cantinieaux et al recently showed that MSC conditioned medium was sufficient to improve recovery after spinal cord injury in a rat model [99]. In a murine model, investigators revealed that MSCs undergoing osteogenic differentiation secreted factors that induced recruitment and differentiation of endogenous progenitor cells [100]. Inhibition of the expression of degrading enzymes and pro-inflammatory cytokines was observed in rat NP cells co-cultured with human synovium-derived MSCs and in a rabbit in vivo model [101].…”

Mesenchymal stromal cells regulate the cell mobility and the immune response during osteogenesis through secretion of vascular endothelial growth factor A

“…The bone regeneration process is controlled by the proliferation, differentiation, migration and apoptosis of various cell types, including osteoblasts, osteoclasts, immune cells and their precursors (Wang et al, ). Although many studies have focused on the ability of implanted cells to differentiate within the defect sites, more recent research suggests other important factors may be involved in bone repair, such as the direct or indirect cell–cell interactions, as well as the release of soluble factors (Li et al, ). However, the molecular mechanisms that contribute to the interaction between host cells, donor cells and immune cells during osteogenesis are poorly understood.…”