Bioceramics of calcium orthophosphates

Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

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Mesenchymal stem cells avoid allogeneic rejection

Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes. Recent studies revealed that human placental membranes are a rich source of MSCs for tissue regeneration and repair. This review provides a concise summary of current knowledge of biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role MSCs have in each phase of the wound-healing process. In addition, characterization of MSCs containing skin substitutes is described, demonstrating the presence of key growth factors and cytokines uniquely suited to aid in wound repair.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.5966/sctm.2011-0018

Concise Review: Role of Mesenchymal Stem Cells in Wound Repair

Natural polymers for gene delivery and tissue engineering

Scar formation, with persistent alteration of the normal tissue structure, is an undesirable and significant result of both wound healing and fibrosing disorders. There are few strategies to prevent or to treat scarring. The transforming growth factor beta (TGF-β) superfamily is an important mediator of tissue repair. Each TGF-β isoform may exert a different effect on wound healing, which may be context-dependent. In particular, TGF-β1 may mediate fibrosis in adults' wounds, while TGF-β3 may promote scarless healing in the fetus and reduced scarring in adults. Thus, TGF-β3 may offer a scar-reducing therapy for acute and chronic wounds and fibrosing disorders.

Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis.

Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy

Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.

Hepatocyte growth factor (HGF) is a ligand for the c‐Met receptor tyrosine kinase. This study was aimed to characterize the role of the HGF gene combined with basic fibroblast growth factor (bFGF) protein in wound healing by administering both of them locally to acute incisional skin wounds created on the backs of rats. The bFGF protein and the HGF gene were administered intradermally after incisional surgery. Apoptotic cells in wound lesions were identified by the terminal deoxynucleotide transferase‐mediated nick‐end labeling method, as well as by immunological detection of active caspase‐3. While there was almost complete suppression of apoptosis with well‐organized wound healing in animals treated with the HGF gene, the combination of bFGF protein and the HGF gene paradoxically resulted in less scarring along with the promotion of apoptosis. Histopathological examination revealed that scar formation was least apparent in rats treated with both bFGF and the HGF gene compared with controls or those treated with the bFGF or the HGF gene alone. It is thought that the combined administration of bFGF and the HGF gene immediately after skin incision may make the healing process occur closer to tissue regeneration through the induction of apoptosis, which occurred 1 week after surgery. HGF supplementation through gene therapy combined with bFGF protein may be an effective strategy for treating wounds, as it increases the apparent regeneration of the dermis to allow for “scarless wound healing.”

Combined administration of basic fibroblast growth factor protein and the hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds: Wound Repair and Regeneration

Hirobumi Hamada

Papers

Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy

Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.

Combined administration of basic fibroblast growth factor protein and the hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds: Wound Repair and Regeneration