Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Abstract

Bone grafting is crucial in the surgical treatment of bone defects and nonunion fractures. Autogenous bone, allogenous bone, and biomaterial scaffold are three main sources of bone grafts. The biomaterial scaffold, both natural and synthetic, is widely accessible but weak in osteogenic potential. One approach to solve this problem is cell-based bone tissue engineering (BTE), established by growing living osteogenic cells on scaffold in vitro to build up its osteoinducitive capability. Mesenchymal stem cell (MSC) is suitable for use in cell-based BTE, but it remains a considerable challenge to induce MSCs to form solely bone and while preventing MSCs from differentiating into fats, muscles, and possibly neural elements in vivo. Recently, there is a drastic rise in use of genetically engineered MSCs, which can secrete growth factors or alter the transcription level, leading to osteoblast lineage commitment, bone formation, fracture repair, and spinal fusion. In this article, we reviewed the literatures regarding applications of genetically engineered MSCs in BTE. We addressed the currently applicable genes and candidate genes for MSCs modification, transduction efficiency and safety issues of the transfect vectors, and administration routes, and we briefly described in vivo tracking and potential clinical application of the genetically modified MSCs in BTE. Anat Rec, 293:531-537, 2010. V V C 2009 Wiley-Liss, Inc.

miR‐182‐5p overexpression inhibits chondrogenesis by down‐regulating PTHLH

“…Previous studies showed that MSC together with bone morphogenic protein 2(BMP‐2) have great potential for repair of bone defects (Chen et al, ). MSCs have the ability to induce bone formation, osteoblast lineage commitment, and fracture repair by secreting growth factors or regulating the transcription level (Hong et al, ). Chondrogenesis of BM‐MSCs is affected by semi‐synthetic biomaterials based on extracellular matrix (ECM) proteins (Goldshmid et al, ).…”

Tissue engineering using 3D printed nano-bioactive glass loaded with NELL1 gene for repairing alveolar bone defects

“…This study adopts the preparation of BG scaffold by the most advanced 3D printing technology, with a multi-layer pore structure and function bearing surface; the BGs can be processed according to particular needs with high accuracy. Moreover, 3D printed BG exhibits significantly improved compressive strength compared with traditional sintered porous hydroxyapatite scaffolds, and the nano structure and the bioactive components loaded by the scaffold efficiently and cooperatively improve bone formation [ 22 ].…”

Adenovirus-mediated bone morphogenetic protein-2 promotes osteogenic differentiation in human mesenchymal stem cells in vitro

“…It is therefore a popular choice for MSCs-based bone tissue engineering. It has been demonstrated that the BMP-2-modified MSCs increase the ALP activity, cell proliferation and mineralization in vitro and heal critical-size bone defects, induce ectopic bone formation, repair fractures and trigger spinal fusion in vivo (29). BMP-2 serves an important role in fracture healing: During the process of bone tissue repair, BMP-2 transmits information between cells and intercellular substances through autocrine and paracrine signaling, regulating the secretion and proliferation of cells.…”