Irradiated Human Chondrocytes Expressing Bone Morphogenetic Protein 2 Promote Healing of Osteoporotic Bone Fracture in Rats

Abstract

Bone morphogenetic protein 2 (BMP2) was selected as a transgene to regenerate osteoporotic bone defects after several BMPs were tested using a bone formation study in nude mice. Human chondrocytes were transduced with a BMP2-containing retroviral vector, and single clones were selected. The cells were characterized over numerous passages for growth and BMP2 expression. The single clones were irradiated and tested for viability. BMP2 expression lasted for 3 weeks before dying off completely after approximately 1 month. Irradiated and non-irradiated transduced chondrocytes successfully healed fractures in osteoporotic rats induced by ovariectomy. The osteoinducing effect of irradiated cells was better than that of their non-irradiated counterparts or a chondrocytes-only control. This study showed that delivering BMP2 from the transduced and irradiated chondrocytes could be an effective and safe method of repairing osteoporotic bone fractures.

Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink

“…6). In agreement with previous findings that the use of irradiation to make chondrocyte replication incompetent also causes apoptosis, all cells were dead within 25 days of irradiation 12 . Fluorescence in situ hybridization (FISH) analysis of the 3D-printed constructs after 5 weeks (Fig.…”

“…5). OCT4 could be detected even in the presence of iChons, which have been shown to produce BMP2 12 , after 1 week of printing when maintained in the conditioned DEF medium. OCT4 signals were not detected after differentiation for 3 or 5 weeks (Fig.…”

“…The positive co-culture effect supported earlier findings that irradiated chondrocytes would stimulate iPSC differentiation by cell-to-cell contact combined with local inherent growth factors 8, 28 . BMP2 has previously been determined to be one of the growth factors secreted by irradiated chondrocytes 12 . By including this morphogene in the chondrogenic differentiation medium, we could enhance the co-culture protocol and detect the differentiation of iPSCs without co-culture.…”

“…Here, we used both iPSCs that originated from chondrocytes and the iPS generation process to rejuvenate the cells into the blastula stage of development, which means that they are pluripotent and can give rise to any cell type in the body, including nerve cells 11 , MSCs or chondrocytes. Differentiation protocols for directing pluripotent stem cells toward the chondrogenic lineage are emerging, and the most robust protocol to date has been co-culturing with chondrocytes mitotically inactivated by irradiation, which are called iChons here and which diminish with time 12 . Newer protocols have emerged, but these include fluorescence-activated cell sorting (FACS), which of course is impossible for encapsulated cells after 3D bioprinting.…”

Orthopedic cellular therapy: An overview with focus on clinical trials

“…Other cell types besides bone marrow derived MSCs, such as umbilical cordderived MSCs (UCBMSCs), adiposederived stem cells (ADSCs), musclederived stem cells and dental pulp derived stem cells were also evaluated [21] . A gene therapy approach also showed osteogenic potential with BMP-2 gene [22] transfected chondrocytes. We believe that the chondrocytes can induce bone formation through the endochondral ossification process.…”