Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor cells for mesenchymal tissues. These cells may also provide a potential therapy for bone repair. Our previous studies showed that MSC engineered with the gene for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were capable of differentiating into osteoblast lineage and inducing autologous bone formation in several animal models. Culturing individual MSC for autologous implantation, however, remains problematic. The number of human MSC with osteogenic potential decreases with age, and, in certain diseases, the patient's marrow may be damaged or the healthy cells reduced in number. In this study, we used rats with a femoral segmental defect to investigate whether allogeneic BMP-2 engineered MSC would facilitate bone healing. We show that BMP-2 engineered allogeneic MSC can repair critical bone defects to the same degree as rats treated with BMP-2 engineered autologous MSC, if the allogeneic group receives short-term treatment with immunosuppressant FK506. We also show that allogeneic gene transferred MSC are directly involved in bone repair, in addition to acting as gene deliverers.

Study Design A study of the morphometrical and histological changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice. Objective In this study we investigate whether the absence of Bgn accelerates the degenerative process in mouse IVD. Summary of Background Data Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD. The ECM of IVD contains several members of the small leucine repeat proteoglycans (SLRPs) family. Bgn is one member of SLRPs family, and showed a unique expression with age and degeneration in the human IVD. To date there have been no in vivo studies to see if SLRPs have a role in maintaining the structural integrity of IVD. To explore the functions of Bgn in the IVD, we examined discs in Bgn-deficient mice. Methods A total of 30 spine specimens were harvested from wild-type (WT) and Bgn-deficient mice. Five specimens for each genotype at 4, 6, and 9 months old were examined in the experiments. Morphometrical and histological analysis of the IVD were performed. Histological gradings were performed separately on nucleus pulposus (NP), annulus fibrosus (AF), and end plate (EP) according to the classification system proposed by Boos et al. Results The Bgn-deficient mice exhibited progressive decreases of NP area with age, which were representative changes consistent with disc degeneration. We found that Bgn-deficient mice developed an early onset of disc degeneration compared to WT mice. The degenerative scores of Bgn-deficient mice were significantly higher than those of WT mice at 4 and 9-month-old. High scores for NP and AF in Bgn-deficient mice significantly affected the difference in total degenerative scores at 9 months of age. Conclusion Bgn deficiency significantly accelerated disc degeneration.

Ageing was found to be the major factor in progressive degeneration of the rotator cuff, and should be considered the single most important contributing factor in the pathogenesis of rotator cuff tears. In addition, degenerative tendonopathy appeared the primary pathology in rotator cuff tear, preceding hypertrophic spur formation. Rotator cuff tears are therefore unlikely to be initiated by impingement; rather, they develop as an intrinsic degenerative tendonopathy.

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