Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model

There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50–150 or 150–250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Selected formulations (1:1 and 3:1 with 50–150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding 1:1 constructs and empty implants by 3- and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlates directly to the DBM dose.     

Imaging and Quantitative Assessment of Long Bone Vascularization in the Adult Rat Using Microcomputed Tomography

The objective of this study was to develop and validate a technique for both 3D imaging and quantification of the vascular network of bone tissue in the rat. Five month‐old male Wistar rats were divided into tail‐suspension (21 days) and control groups. Sixty percent barium sulfate solution was infused into the vena cava. The tibiae were evaluated in 2D and 3D before and after decalcification, using conventional microcomputerized tomography (μCT) at 10 and 5 μm resolution and synchrotron radiation (SR) μCT. The perfusion technique and tomography exhibited excellent bone vasculature imaging. Significant positive correlations were observed between 2D histomorphometric and 3D μCT vascular parameters (P < 0.05). 3DμCT discriminated significant changes of vessel structures in unloading condition: vessel number decreased by 25%, (P < 0.005), vessel separation increased by 27%, P < 0.01. SRμCT could image sinusoid clusters in bone. μCT is an accurate and reproducible technique for 3D quantitative evaluation of long bone vascularisation in the rat. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.     

Hydrophobicity as a design criterion for polymer scaffolds in bone tissue engineering

Porous polymeric scaffolds play a key role in most tissue-engineering strategies. A series of non-degrading porous scaffolds was prepared, based on bulk-copolymerisation of 1-vinyl-2-pyrrolidinone (NVP) and n-butyl methacrylate (BMA), followed by a particulate-leaching step to generate porosity. Biocompatibility of these scaffolds was evaluated in vitro and in vivo. Furthermore, the scaffold materials were studied using the so-called demineralised bone matrix (DBM) as an evaluation system in vivo. The DBM, which is essentially a part of a rat femoral bone after processing with mineral acid, provides a suitable environment for ectopic bone formation, provided that the cavity of the DBM is filled with bone marrow prior to subcutaneous implantation in the thoracic region of rats. Various scaffold materials, differing with respect to composition and, hence, hydrophilicity, were introduced into the centre of DBMs. The ends were closed with rat bone marrow, and ectopic bone formation was monitored after 4, 6, and 8 weeks, both through X-ray microradiography and histology. The 50:50 scaffold particles were found to readily accommodate formation of bone tissue within their pores, whereas this was much less the case for the more hydrophilic 70:30 counterpart scaffolds. New healthy bone tissue was encountered inside the pores of the 50:50 scaffold material, not only at the periphery of the constructs but also in the center. Active osteoblast cells were found at the bone-biomaterial interfaces. These data indicate that the hydrophobicity of the biomaterial is, most likely, an important design criterion for polymeric scaffolds which should promote the healing of bone defects. Furthermore, it is argued that stable, non-degrading porous biomaterials, like those used in this study, provide an important tool to expand our comprehension of the role of biomaterials in scaffold-based tissue engineering approaches.     

Reconstruction of cartilage,bone, and hematopoietic microenvironment with demineralized bone matrix and bone marrow cells

Highly specialized hard tissues, such as cartilage, bone, and stromal microenvironment supporting hematopoiesis, originate from a common type of mesenchymal progenitor cell (MPC). We hypothesized that MPCs present in bone marrow cell suspension and demineralized bone matrix (DBM) that possess natural conductive and inductive features might constitute a unit containing all the essential elements for purposive bone and cartilage induction. Using a rodent preclinical model, we found that implantation of a composite comprising DBM and MPCs into A) a damaged area of a joint; B) an ablated bone marrow cavity, and C) a calvarial defect resulted in the generation of A) a new osteochondral complex comprising articular cartilage and subchondral bone; B) trabecular bone and stromal microenvironment supporting hematopoiesis, and C) flat bone, respectively. The new tissue formation followed differentiation pathways controlled by site-specific physiological conditions, thus developing tissues that precisely met local demands.     

An image-based skeletal dosimetry model for the ICRP reference adult male--internal electron sources

In this study, a comprehensive electron dosimetry model of the adult male skeletal tissues is presented. The model is constructed using the University of Florida adult male hybrid phantom of Lee et al (2010 Phys. Med. Biol. 55 339-63) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex available from http://stacks.iop.org/0031-9155/56/2309/mmedia. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, is imposed through detailed analyses of whole-body ex vivo CT images (1 mm resolution) and spongiosa-specific ex vivo microCT images (30 μm resolution), respectively, taken from a 40 year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP's change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10 μm endosteal layer covering the trabecular and cortical surfaces to a 50 μm shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal-averaged values of absorbed fraction in the present model are noted to be very compatible with those weighted by the skeletal tissue distributions found in the ICRP Publication 110 adult male and female voxel phantoms, but are in many cases incompatible with values used in current and widely implemented internal dosimetry software.     

Calcium sulfate-carboxymethylcellulose bone graft binder: Histologic and morphometric evaluation in a critical size defect

Calcium sulfate (CS) is widely used as a bone graft binder and expander. Recent reports indicate that carboxymethylcellulose (CMC) can improve the clinical properties of CS when used as binder for particulate bone grafts; however, limited information is available on the effects of CMC on bone regeneration. The purpose of this study was to evaluate the histologic and morphometric characteristics of bone formation in calvarial defects grafted with a CS-based putty containing 10% CMC in combination with allogeneic demineralized bone matrix (DBM). Bone formation and graft/binder resorption were compared with a surgical grade CS and DBM in paired critical-sized calvarial defects in 25 Wistar rats (350-450 g). Six animals each provided paired defects at 7, 14, 21, and 28 days postsurgery for nondecalcified processing and microscopic analysis. Defects grafted with CS or CS-CMC putty as the DBM binder exhibited similar patterns and proportions of bone formation, fibrous tissue/marrow, and residual DBM particles. Comparable mean +/- SD proportions of new bone formation (31.7 +/- 9.5 and 33.7 +/- 12.9), fibrous tissue/marrow (54.2 +/- 8.3 and 53.0 +/- 10.8), residual DBM particles (8.3 +/- 6.8 and 10.1 +/- 6.3), and residual binder material (5.5 +/- 4.6 and 3.7 +/- 3.5) were found at 28 days for defects grafted with CS and CS-CMC putty, respectively. Thus, CMC was found to improve the handling characteristics of CS and, when used in conjunction with DBM, supported comparable levels bone formation and patterns of binder/scaffold resorption as CS and DBM in a calvarial defect model.     

A composite demineralized bone matrix – Self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow

The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic.     

The promotion of the vascularization of decalcified bone matrix in vivo by rabbit bone marrow mononuclear cell-derived endothelial cells

The neovascularization of bone grafting represents an important challenge in bone regeneration. Prevascularization of tissue-engineered bone using endothelial cells (ECs) in vitro sheds light on accelerating the vascularization of bone replacements. In the present study, decalcified bone matrix (DBM) was prevascularized by seeding fibrin gels with ECs that are derived from rabbit bone marrow mononuclear cells (BMMNCs). The compound was then transplanted autologously into bone defects of rabbits to observe the vascularization in vivo. At 2, 4 and 8 weeks after grafting, the microvessel density of new bone tissues was significantly higher in the experimental group than in the control group (P < 0.05), which suggests that prevascularization of BMMNC-derived cells may be suitable for improving vascularization in tissue-engineered bone.     

Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect

Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.     

Nell-1 protein promotes bone formation in a sheep spinal fusion model

Bone morphogenetic proteins (BMPs) are widely used as bone graft substitutes in spinal fusion, but are associated with numerous adverse effects. The growth factor Nel-like molecule-1 (Nell-1) is mechanistically distinct from BMPs and can minimize complications associated with BMP therapies. This study evaluates the efficacy of Nell-1 combined with demineralized bone matrix (DBM) as a novel bone graft material for interbody spine fusion using sheep, a phylogenetically advanced animal with biomechanical similarities to human spine. Nell-1+sheep DBM or Nell-1+heat-inactivated DBM (inDBM) (to determine the osteogenic effect of residual growth factors in DBM) were implanted in surgical sites as follows: (1) DBM only (control) (n=8); (2) DBM+0.3?mg/mL Nell-1 (n=8); (3) DBM+0.6?mg/mL Nell-1 (n=8); (4) inDBM only (control) (n=4); (5) inDBM+0.3?mg/mL Nell-1 (n=4); (6) inDBM+0.6?mg/mL Nell-1 (n=4). Fusion was assessed by computed tomography, microcomputed tomography, and histology. One hundred percent fusion was achieved by 3 months in the DBM+0.6?mg/mL Nell-1 group and by 4 months in the inDBM+0.6?mg/mL Nell-1 group; bone volume and mineral density were increased by 58% and 47%, respectively. These fusion rates are comparable to published reports on BMP-2 or autograft bone efficacy in sheep. Nell-1 is an independently potent osteogenic molecule that is efficacious and easily applied when combined with DBM.     

Performance evaluation of density measurements of axial and peripheral bone with x-ray and gamma-ray computed tomography

We examined sources of error in bone measurements made with computed tomography (CT) using a whole-body scanner (GE 8800) and a peripheral-bone CT scanner (developed at the University of Alberta). We investigated the influence of various factors on trabecular bone density: homogeneity and noise in the image plane, linearity of calibration, body size, effects of cortical bone, and the image analysis procedure. With the GE 8800 scanner, the precision (SD) of measurements of a single vertebra is expected to be +/- 1.65% (noise: +/- 0.22%, calibration: +/- 1.3%, analysis: +/- 1%); the accuracy, excluding consideration of marrow fat, varied between -2.7 and +7.3% (compact-bone thickness: 2-5%, body size: -2.5 - +1.5%, calibration: -0.47 - +0.77%). With the peripheral-bone CT scanner, the total precision error (+/- 0.53%) was dominated by noise, with only a minor contribution from the analysis procedure (+/- 0.04%); accuracy varied between -0.6 and +3.4% (effect of cortical bone: up to 3.0%; changes in size of object: -0.59 - +0.4%). The magnitude of these errors was determined under 'ideal' conditions, mostly through phantom measurements; therefore, the errors represent optimistic lower limits in clinical application. Furthermore, measurements of density of cortical bone were not reliable for bone thicknesses of less than about 4 mm with the GE 8800 scanner and less than about 1.5 mm with the peripheral scanner.     

Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells

We examined whether transplantation of autologous bone marrow mononuclear cells (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast growth factor (bFGF) were prepared for the controlled release of bFGF. To evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent-labeled autologous BM-MNCs together with gelatin microspheres containing 10 microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs expressed CD31, an endothelial lineage cell marker, and induced efficient neovascularization at the implanted site 2 weeks after implantation. Capillary density in Col + BM-MNCs + bFGF was significantly large compared with other groups. This combination also enhanced regeneration of the bone defect after 8 weeks to a significantly greater extent than either BM-MNCs or bFGF on their own. In summary, these findings demonstrate that a combination of BM-MNCs and bFGF gelatin hydrogel enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration.     

Evaluation of bone regeneration at critical-sized calvarial defect by DBM/AM composite

This study investigated the bone-regenerative potential of a demineralized bone and acellular matrix (DBM/AM) composite (AlloCraft DBM) in comparison with autologous bone using an in vivo model. Critical-sized calvarial defects (5 mm) were created in athymic rats. The defects were grafted with either the DBM/AM composite or the acellular human dermal matrix (AM), and compared with the defects filled with autologous bone (positive control) and the empty defect (negative control). Histological and radiographic assessments were carried out at 4 and 8 weeks after surgery to determine the biological healing, the amount and type of new bone formation and the percentage of new bone filled in the critical defects. At 4 weeks, DBM/AM composite group had the highest percentage of the defect filled with new bone (84%), which was significantly greater than autologous bone (62%), AM (41%), and untreated control (32%) groups. At 8 weeks, the DBM/AM continued to have the highest percentage of the defect filled with new bone (91%). The autologous bone group increased the percentage of bone fill to 83%. The defects either filled with AM or left untreated still had less of the defect filled with new bone, 57% and 33%, respectively. The total healing of defects grafted with DBM/AM was comparable with autologous bone group at 8 weeks. The results demonstrated that the DBM/AM composite promoted new bone formation more rapidly than autologous bone at calvarial defect in athymic rats. The study supports that DBM/AM is a potential substitute of autologous bone for bone repair.     

Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons

Two skeletal dosimetry methods using μCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic–periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use μCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 μm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the μCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger μCT images of TB.     

A reducible polycationic gene vector derived from thiolated low molecular weight branched polyethyleneimine linked by 2-iminothiolane

To improve transfection efficiency and reduce the cytotoxicity of polymeric gene vectors, reducible polycations (RPC) were synthesized from low molecular weight (MW) branched polyethyleneimine (bPEI) via thiolation and oxidation. RPC (RPC-bPEI(0.8 kDa)) possessed MW of 5 kDa-80 kDa, and 50%-70% of the original proton buffering capacity of bPEI(0.8 kDa) was preserved in the final product. The cytotoxicity of RPC-bPEI(0.8 kDa) was 8-19 times less than that of the gold standard of polymeric transfection reagents, bPEI(25 kDa). Although bPEI(0.8 kDa) exhibited poor gene condensing capacities (～2 μm at a weight ratio (WR) of 40), RPC-bPEI(0.8 kDa) effectively condensed plasmid DNA (pDNA) at a WR of 2. Moreover, RPC-bPEI(0.8 kDa)/pDNA (WR ≥2) formed 100-200 nm-sized particles with positively charged surfaces (20-35 mV). In addition, the results of the present study indicated that thiol/polyanions triggered the release of pDNA from RPC-bPEI(0.8 kDa)/pDNA via the fragmentation of RPC-bPEI(0.8 kDa) and ion-exchange. With negligible polyplex-mediated cytotoxicity, the transfection efficiencies of RPC-bPEI(0.8 kDa)/pDNA were approximately 1200-1500-fold greater than that of bPEI(0.8 kDa)/pDNA and were equivalent or superior (～7-fold) to that of bPEI(25 kDa)/pDNA. Interestingly, the distribution of high MW RPC-bPEI(0.8 kDa)/pDNA in the nucleus of the cell was higher than that of low MW RPC-bPEI(0.8 kDa)/pDNA. Thus, the results of the present study suggest that RPC-bPEI(0.8 kDa) has the potential to effectively deliver genetic materials with lower levels of toxicity.     

The skeleton as a unique environment for breast cancer cells

Bone is a favored location for several cancer metastases especially breast, prostate and myeloma. This review evaluates various properties of the skeleton that contribute to its successful colonization by breast cancer cells. The first consideration is the unique aspects of the vasculature of metaphyseal bone, which may account for the initial lodging of breast cancer cells in specific regions of the skeleton. Metasphyseal bone, found at the ends of long bone, in ribs and in vertebrae, is comprised of trabecular bone interspersed with marrow and a rich vasculature. The chemotactic factors that arise from bone marrow and bone cells are discussed in terms of cancer cell migration out of the vasculature and entry of cancer cells into the marrow cavity. Once the breast cancer cells have migrated into the metaphysis, they interact both directly and indirectly with bone cells and other cells in the marrow. As tumor growth progresses, functional bone cells are lost, most likely through apoptosis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration.

Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. Its expression is most prominent during the late stages of vascular development and in the adult vasculature. Our previous studies have shown that TSP1 expression promotes a quiescent, differentiated phenotype of vascular endothelial cells. However, the physiological role TSP1 plays during vascular development and neovascularization requires further delineation. Here, we investigated the role of TSP1 during development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy. The retinal vascular density was increased in TSP1-deficient (TSP1-/-) mice compared with wild-type mice. This finding was mainly attributed to increased number of retinal endothelial cells in TSP1-/- mice. During oxygen-induced ischemic retinopathy, the developing retinal vasculature of TSP1-/- mice was less sensitive to vessel obliteration induced by hyperoxia but exhibited a similar level of neovascularization induced by normoxia compared with wild-type mice. This finding is consistent with the similar pattern of VEGF expression detected in wild-type and TSP1-/- mice. Furthermore, the increased expression of TSP1 during development of retinal vasculature was not affected by oxygen-induced ischemic retinopathy. In addition, the regression of ocular embryonic (hyaloid) vessels, as well as the newly formed retinal vessels during oxygen-induced ischemic retinopathy, was delayed in TSP1-/- mice. Therefore, TSP1 is a modulator of vascular homeostasis and its expression is essential for appropriate remodeling and maturation of retinal vasculature.     

The bone marrow constitutes a reservoir of pericyte progenitors

Adult bone marrow is a rich reservoir of hematopoietic and mesenchymal stem and progenitor cells. Mobilization and recruitment of bone marrow-derived cells to injured or ischemic tissue or tumors endorse the initiation and maintenance of angiogenic processes in the adult by incorporating endothelial progenitor cells (EPC) into the developing vasculature and by recruiting accessory hematopoietic cells. Recent data have now revealed that the origin of bone marrow-derived vascular cells is not restricted to endothelial cells but also includes pericytes--the perivascular support cells. Several laboratories have now reported the existence of pericyte progenitor cells, and these cells, like EPC, can be mobilized and recruited to the remodeling vasculature under ischemic conditions and in tumors. This review focuses on pericytes in vessel formation and on recent discoveries about their bone marrow origin in the adult.     

成人正常胸、腰椎体双源双能CT虚拟去钙骨髓成像量化标准值研究

目的 探讨成人正常胸、腰椎体双源双能CT虚拟去钙(VNCa)骨髓成像的量化标准值。方法 对2016年8—11月山东大学齐鲁医院200名正常体检者进行前瞻性胸、腰椎双源双能量CT扫描,按年龄、性别分为<45岁的男性和女性组以及≥45岁的男性和女性组,4组各50人。在虚拟去钙技术下,测量获得T₃~L₅各椎体的骨髓CT值,再根据测得的各椎体的骨髓CT值的相近程度分成T₃~T₅、T₆~T₉、T₁₀~L₁、L₂~L₅ 4部分并取均值,采用独立样本t检验探讨上述测量参数在不同年龄分组及性别分组之间的差异。结果 ＜45岁组胸、腰椎的骨髓CT值分别为(-29.00±10.62)HU、(-35.81±12.36)HU,均高于≥45岁组的(-41.67±17.16)HU、(-44.81±14.35)HU,差异均有统计学意义(t=-6.326、-4.746,P值均<0.01)。<45岁女性组胸、腰椎的骨髓CT值分别为(-27.76±9.55)HU、(-37.56±9.05)HU,均分别高于≥45岁女性组的(-37.80±15.97)HU、(-45.45±14.04)HU,差异均有统计学意义(t=3.818、3.339,P值均＜0.01);<45岁男性组胸、腰椎的骨髓CT值分别为(-30.73±12.16)HU、(-33.91±14.64)HU,均分别高于≥45岁男性组的(-46.07±17.42)HU、(-44.68±14.84)HU,差异均有统计学意义(t=5.105、3.653,P值均＜0.05);<45岁组的男、女性的胸椎骨髓CT值比较差异无统计学意义(P＞0.05),但≥45岁组的男、女性的胸椎骨髓CT值比较差异有统计学意义(t=2.474,P＜0.05);<45岁组和≥45岁组的男、女性间腰椎的骨髓CT值比较,差异均无统计学意义(P值均＞0.05)。观察对象胸、腰椎体的骨髓CT值均与年龄呈负相关(r=-0.463、-0.402,P值均＜0.01)。对于T₃~T₅、T₆~T₉、T₁₀~L₁、L₂~L₅ 4段椎体平均骨髓CT值而言,<45岁组的各段骨髓CT值均高于≥45岁组的骨髓CT值(P值均＜0.01);不同性别间比较,仅≥45岁组的T₆~T₉、T₁₀~L₁椎体节段骨髓CT值比较差异有统计学意义(t=3.177、-2.326,P值均＜0.05)。本组检测者CT辐射剂量容积CT剂量指数和剂量长度乘积分别为4.53～18.79(8.73±2.98)mGy和117.34～1678.42(421.53±230.85)mGy·cm,有效辐射剂量为(6.35±3.43) mSv。结论 正常人胸、腰椎双源双能VNCa骨髓成像的量化CT值较为稳定,可为椎体疾病的诊断提供客观的量化标准值,且其辐射剂量值并未增加甚至降低。