• Aortic Calcification and Femoral Bone Density Are Independently Associated with Left Ventricular Mass in Patients with Chronic Kidney Disease

      Chue, Colin D.; Wall, Nadezhda A.; Crabtree, Nicola J.; Zehnder, Daniel; Moody, William E.; Edwards, Nicola C.; Steeds, Richard P.; Townend, Jonathan N.; Ferro, Charles J.; Shi, Xing-Ming; et al. (2012-06-18)
      Background: Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study.
    • The Early Stage Adjacent Disc Degeneration after Percutaneous Vertebroplasty and Kyphoplasty in The Treatment of Osteoporotic VCFs

      Qian, Jun; Yang, Huilin; Jing, Juehua; Zhao, Hong; Ni, Li; Tian, Dasheng; Wang, Zhengfei; Shi, Xing-Ming; Department of Pathology; College of Graduate Studies (2012-10-8)
      Background: The purpose of this paper is to determine the early incidence of disc de- generation adjacent to the vertebral body of osteoporotic fracture treated with percutaneous vertebroplasty or balloon kyphoplasty and whether adjacent disc degeneration is accelerated by this two procedures.
    • Isolation of Osteoprogenitors from Human Jaw Periosteal Cells: A Comparison of Two Magnetic Separation Methods

      Olbrich, Marcus; Rieger, Melanie; Reinert, Siegmar; Alexander, Dorothea; Department of Pathology; College of Graduate Studies (2012-10-19)
      Human jaw periosteum tissue contains osteoprogenitors that have potential for tissue engineering applications in oral and maxillofacial surgeries. To isolate osteoprogenitor cells from heterogeneous cell populations, we used the specific mesenchymal stem cell antigen-1 (MSCA-1) antibody and compared two magnetic separation methods. We analyzed the obtained MSCA-1+ and MSCA-1â fractions in terms of purity, yield of positive/negative cells and proliferative and mineralization potentials. The analysis of cell viability after separation revealed that the EasySep method yielded higher viability rates, whereas the flow cytometry results showed a higher purity for the MACS-separated cell fractions. The mineralization capacity of the osteogenic induced MSCA-1+ cells compared with the MSCA-1â controls using MACS was 5-fold higher, whereas the same comparison after EasySep showed no significant differences between both fractions. By analyzing cell proliferation, we detected a significant difference between the proliferative potential of the osteogenic cells versus untreated cells after the MACS and EasySep separations. The differentiated cells after MACS separation adjusted their proliferative capacity, whereas the EasySep-separated cells failed to do so. The protein expression analysis showed small differences between the two separation methods. Our findings suggest that MACS is a more suitable separation method to isolate osteoprogenitors from the entire jaw periosteal cell population.
    • Ontological Differences in First Compared to Third Trimester Human Fetal Placental Chorionic Stem Cells

      Jones, Gemma N.; Moschidou, Dafni; Puga-Iglesias, Tamara-Isabel; Kuleszewicz, Katarzyna; Vanleene, Maximilien; Shefelbine, Sandra J.; Bou-Gharios, George; Fisk, Nicholas M.; David, Anna L.; De Coppi, Paolo; et al. (2012-09-4)
      Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold promise for use in tissue engineering applications and cell-based therapies, but their collection is restricted ethically and technically. In contrast, the placenta is a potential source of readily-obtainable stem cells throughout pregnancy. In fetal tissues, early gestational stem cells are known to have advantageous characteristics over neonatal and adult stem cells. Accordingly, we investigated whether early fetal placental chorionic stem cells (e-CSC) were physiologically superior to their late gestation fetal chorionic counterparts (l-CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating down the osteogenic, adipogenic and neurogenic pathways, and containing a subset of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an array of genes expressed in pluripotent stem cells and primordial germ cells, including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS, NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an earlier state of stemness compared to l-CSC, such as smaller size, faster kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not l-CSC, formed embryoid bodies containing cells from the three germ layer lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo; when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC increased bone quality and plasticity; and when applied to a skin wound, e-CSC, but not l-CSC, accelerated healing compared to controls. Our results provide insight into the ontogeny of the stemness phenotype during fetal development and suggest that the more primitive characteristics of early compared to late gestation fetal chorionic stem cells may be translationally advantageous.
    • The Transcriptional Profile of Mesenchymal Stem Cell Populations in Primary Osteoporosis Is Distinct and Shows Overexpression of Osteogenic Inhibitors

      Benisch, Peggy; Schilling, Tatjana; Klein-Hitpass, Ludger; Frey, Sonke P.; Seefried, Lothar; Raaijmakers, Nadja; Krug, Melanie; Regensburger, Martina; Zeck, Sabine; Schinke, Thorsten; et al. (2012-09-24)
      Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79â 94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of â ¼30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP.