Genetically engineered mesenchymal stem cells: applications in spine therapy.

Spine disorders and intervertebral disc degeneration are considered the main causes for the clinical condition commonly known as back pain. Spinal fusion by implanting autologous bone to produce bony bridging between the two vertebrae flanking the degenerated-intervertebral disc is currently the most efficient treatment for relieving the symptoms of back pain. However, donor-site morbidity, complications and the long healing time limit the success of this approach.

Maxillofacial-derived stem cells regenerate critical mandibular bone defect.

Stem cell-based bone tissue regeneration in the maxillofacial complex is a clinical necessity. Genetic engineering of mesenchymal stem cells (MSCs) to follow specific differentiation pathways may enhance the ability of these cells to regenerate and increase their clinical relevance. MSCs isolated from maxillofacial bone marrow (BM) are good candidates for tissue regeneration at sites of damage to the maxillofacial complex.

Molecular targets for tendon neoformation.

Tendons and ligaments are unique forms of connective tissue that are considered an integral part of the musculoskeletal system. The ultimate function of tendon is to connect muscles to bones and to conduct the forces generated by muscle contraction into movements of the joints, whereas ligaments connect bone to bone and provide joint stabilization. Unfortunately, the almost acellular and collagen I-rich structure of tendons and ligaments makes them very poorly regenerating tissues.

Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the regulation of bone formation.

Unlabelled: A bioinformatics-based analysis of endochondral bone formation model detected several genes upregulated in this process. Among these genes the dickkopf homolog 3 (Dkk3) was upregulated and further studies showed that its expression affects in vitro and in vivo osteogenesis. This study indicates a possible role of Dkk3 in regulating bone formation.

Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration.

There are several gene therapy approaches to tissue regeneration. Although usually efficient, virusbased approaches may elicit an immune response against the viral proteins. An alternative approach, nonviral transfer, is safer, and can be controlled and reproduced.

Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells.

The culture expansion of human mesenchymal stem cells (hMSCs) may alter their characteristics and is a costly and time-consuming stage. This study demonstrates for the first time that immunoisolated noncultured CD105-positive (CD105(+)) hMSCs are multipotent in vitro and exhibit the capacity to form bone in vivo. hMSCs are recognized as promising tools for bone regeneration.

Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness.

Infusion of either embryonic or mesenchymal stem cells prolongs the survival of organ transplants derived from stem cell donors and prevents graft-versus-host-disease (GVHD). An in-depth mechanistic understanding of this tolerization phenomenon could lead to novel cell-based therapies for transplantation. Here we demonstrate that while human mesenchymal stem cells (hMSCs) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APCs; either monocytes or dendritic cells) to the cultures inhibits the T-cell responses.

Cell-mediated gene therapy for bone formation and regeneration.

Cell-mediated gene therapy is one of the new modalities branching out from the wide-ranging field of gene transfer and therapy. When applied to bone formation and regeneration, it has particular advantages depending on the type of cell used as a platform for gene delivery. When utilizing adult mesenchymal stem cells or osteoprogenitor cells for the expression of bone-promoting osteogenic factors, the cells not only express the factors promoting bone growth, but can respond, differentiate and participate in the bone formation process.