Paul Schumann

Publications of Paul Schumann

• Increase in periosteal angiogenesis through heat shock conditioning.

  Authors: Majeed Rana, Constantin von See, Martin Rücker, Paul Schumann, Harald Essig, Horst Kokemüller, Daniel Lindhorst, Nils-Claudius Gellrich

  Head & face medicine. 11/2011; 7:22.

  It is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-termIt is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-term effects of stress conditioning on microcirculation, especially on the microcirculation of the periosteum of the calvaria. For this reason, we used intravital fluorescence microscopy to investigate the effects of heat shock priming on the microcirculation of the periosteum over a period of several days. Fifty-two Lewis rats were randomized into eight groups. Six groups underwent heat shock priming of the periosteum of the calvaria at 42.5°C, two of them (n = 8) for 15 minutes, two (n = 8) for 25 minutes and two (n = 8) for 35 minutes. After 24 hours, a periosteal chamber was implanted into the heads of the animals of one of each of the two groups mentioned above. Microcirculation and inflammatory responses were studied repeatedly over a period of 14 days using intravital fluorescence microscopy. The expression of heat shock protein (HSP) 70 was examined by immunohistochemistry in three further groups 24 hours after a 15-minute (n = 5), a 25-minute (n = 5) or a 35-minute (n = 5) heat shock treatment. Two groups that did not undergo priming were used as controls. One control group (n = 8) was investigated by intravital microscopy and the other (n = 5) by immunohistochemistry. During the entire observation period of 14 days, the periosteal chambers revealed physiological microcirculation of the periosteum of the calvaria without perfusion failures. A significant (p < 0.05) and continuous increase in functional capillary density was noted from day 5 to day 14 after 25-minute heat shock priming. Whereas a 15-minute exposure did not lead to an increase in functional capillary density, 35-minute priming caused a significant but reversible perfusion failure in capillaries. Non-perfused capillaries in the 35-minute treatment group were reperfused by day 10. Immunohistochemistry demonstrated an increase in cytoprotective HSP70 expression in the periosteum after a 15-minute and a 35-minute heat shock pretreatment when compared with the control group. The level of HSP70 expression that was measured in the periosteum after 25 minutes of treatment was significantly higher than the levels observed after 15 or 35 minutes of heat shock exposure. A few days after heat shock priming over an appropriate period of time, a continuous increase in functional capillary density is seen in the periosteum of the calvaria. This increase in perfusion appears to be the result of the induction of angiogenesis.

• Calvaria bone chamber--a new model for intravital assessment of osseous angiogenesis.

  Authors: Branko Sinikovic, Paul Schumann, Meike Winkler, Julian Kuestermeyer, Frank Tavassol, Constantin von See, Carlos Carvalho, Rolf Mülhaupt, Kai-Hendrik Bormann, Horst Kokemueller, Andrea Meyer-Lindenberg, Matthias W Laschke, Michael D Menger, Nils-Claudius Gellrich, Martin Rücker

  Journal of biomedical materials research. Part A. 11/2011; 99(2):151-7.

  The faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation ofThe faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation of angiogenesis are described, none of them allows the observation of new vessel formation in desmal bone. Therefore, we developed a new chamber model suitable for quantitative in vivo assessment of the vascularization of bone substitutes by intravital fluorescence microscopy. In the parietal calvaria of 32 balb/c mice a critical size defect was set. Porous 3D-poly(L-lactide-co-glycolide) (PLGA)-blocks were inserted into 16 osseous defects (groups 3 and 4) while other 16 osseous defects remained unequipped (groups 1 and 2). By placing a polyethylene membrane onto the dura mater, the angiogenesis was mainly restricted to the osseous margins (groups 2 and 4). Microvascular density, angiogenesis, and microcirculatory parameters were evaluated repetitively during 22 days. In all animals, only a mild inflammatory reaction was observed with a climax after 2 weeks. The implantation of PLGA scaffolds resulted in a vascular growth directed towards the center of the defect as demonstrated by the significantly (p < 0.05) enhanced central microvascular densitiy from day 3 to day 22 when compared with unequipped chambers. The additional application of polyethylene membrane was found to reduce significantly the microvessel density mainly in the center of both scaffolds and defects. The present calvaria bone chamber allows for the first time to assess quantitatively the angiogenesis arising from desmal bone directly in vivo. Therefore, this chronic model may support the future research in the biological adequacy of bone substitutes.

• A novel approach for studying microcirculation in bone defects by intravital fluorescence microscopy.

  Authors: Frank Tavassol, Andreas Kampmann, Paul Schumann, Daniel Lindhorst, Horst Kokemüller, Harald Essig, Jan-Helge Meemken, Martin Rücker, Nils-Claudius Gellrich

  Tissue engineering. Part C, Methods. 07/2011; 17(12):1151-9.

  Angiogenic and inflammatory responses to biodegradable scaffolds were previously studied using the dorsal skinfold chamber for testing different scaffold materials. In this model, the angiogenicAngiogenic and inflammatory responses to biodegradable scaffolds were previously studied using the dorsal skinfold chamber for testing different scaffold materials. In this model, the angiogenic response originates from the soft tissue of the skin. Herein, we introduce a new model that allows the study of developing microcirculation of bone defects for testing tissue-engineered constructs. A bone defect was prepared in the femur of Balb/c mice by inserting a pin for intramedullary fixation, and a custom-made observation window fixed over the defect allowed constant observation. This study included three different groups: empty defect (control), defect filled with porous poly(L-lactide-co-glycolide), and beta-tricalcium-phosphate scaffolds. Starting from 6 days after surgery, angiogenesis, neovascularization, leukocyte-endothelial cell interaction, and microvascular permeability were analyzed over 22 days by using intravital fluorescence microscopy. The empty defects showed no signs of angiogenesis during the observation period, but a distinct increase of capillary density was detected in the scaffold-containing defects. Surprisingly, the histological sections of the scaffold-treated defects showed new bone formation 22 days after implantation. We present a new bone chamber model for intravital long-term study of scaffold materials suitable for bone reconstruction in mice by using fluorescence microscopy.

• Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs.

  Authors: Paul Schumann, Constantin von See, Andreas Kampmann, Daniel Lindhorst, Frank Tavassol, Horst Kokemüller, Kai-Hendrik Bormann, Nils-Claudius Gellrich, Martin Rücker

  Journal of biomedical materials research. Part A. 04/2011; 97(4):383-94.

  The demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineeringThe demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineering constructs is a limited vascularization. In an attempt to accelerate the vascularization of tissue engineering constructs we compared the usage of bone marrow mesenchymal stem cells (bmMSCs) and fragments derived from the aorta in vivo. Tissue engineering constructs composed of PLGA scaffolds containing Matrigel (n = 8), aortic fragments embedded in Matrigel (n = 8), bmMSCs embedded in Matrigel (n = 8), and aortic fragments embedded in Matrigel combined with bmMSCs (n = 8) were implanted into dorsal skinfold chambers of balb/c mice and analyzed repetitively over 14 days. In all groups a weak inflammatory response was transiently apparent. Vascularization was significantly (p = 0.05) accelerated in bmMSC and aortic fragments containing constructs compared with Matrigel alone, demonstrated by a distinctly increased microvascular density throughout the whole experiment. The combination of bmMSCs and aortic fragments showed no additional effect compared with bmMSCs and aortic fragments alone. The accelerated vascularization and microvascular density of tissue engineering constructs triggered by bmMSCs and aortic fragments is comparable. Thus aortic fragments provide a new promising source for clinical relevant tissue engineering constructs.

• Prolongated survival of osteoblast-like cells on biodegradable scaffolds by heat shock preconditioning.

  Authors: Frank Tavassol, Andreas Kampmann, Daniel Lindhorst, Paul Schumann, Horst Kokemüller, Kai-Hendrik Bormann, Nils-Claudius Gellrich, Martin Rücker

  Tissue engineering. Part A. 03/2011; 17(15-16):1935-43.

  The implantation of tissue-engineered constructs leads to hypoxic and physical stress to the seeded cells until they were reached by a functional microvascular system. Preconditioning of cells withThe implantation of tissue-engineered constructs leads to hypoxic and physical stress to the seeded cells until they were reached by a functional microvascular system. Preconditioning of cells with heat shock induced heat shock proteins, which can support the cells to survive a subsequent episode of stress that would otherwise be lethal. Preconditioning of tissue-engineered constructs resulted in significantly higher number of surviving osteoblast-like cells (OLC). At the 6th and 10th day, angiogenic response was found comparative to poly(L-lactide-co-glycolide) (PLGA) scaffolds vitalized with either unconditioned or preconditioned OLC. However, they were significantly enhanced compared with the nonvitalized collagen-labeled PLGA scaffolds. This study demonstrates that vitalization of PLGA scaffolds with OLC accelerates the angiogenic response induced by the surrounding host tissue. In addition, heat shock preconditioning significantly enhances the survival rate of the OLC that are seeded on these scaffolds. Thus, vitalization of substitutes with adequately pretreated OLC may promise biologically adequate osseous restorations.

• The Hannover experience: surgical treatment of tongue cancer--a clinical retrospective evaluation over a 30 years period.

  Authors: Horst Kokemueller, Majeed Rana, Jennifer Rublack, Andre Eckardt, Frank Tavassol, Paul Schumann, Daniel Lindhorst, Martin Ruecker, Nils-Claudius Gellrich

  Head & neck oncology. 01/2011; 3:27.

  In this retrospective study, we present a clinical review of our experience with tongue cancer in order to obtain valid criteria for therapeutic decision-making. Between 1980 and 2009, a total of 341In this retrospective study, we present a clinical review of our experience with tongue cancer in order to obtain valid criteria for therapeutic decision-making. Between 1980 and 2009, a total of 341 patients with squamous cell carcinoma of the tongue were treated at our Department. The average follow-up was 5.2 years. 309 patients received surgical treatment, which was combined in nearly 10% with neoadjuvant and in nearly 20% with postoperative radio(chemo)therapy. 32 patients were excluded from surgery and received primary radiation. Local and regional failure occurred in 23.9% and 20.4%, leading to a total failure rate of 37.2% after an average duration of 1,6 years. N-Status, extracapsular spread and clear margins were identified as the dominant factors for survival, which was calculated with 54.5% after 5 years. We recommend categorical bilateral neck dissection in order to reliably remove occult lymph node metastases. Adjuvant treatment modalities should be applied more frequently in controlled clinical trials and should generally be implemented in cases with unclear margins and lymphatic spread. This study provides new treatment strategies for primary tumour disease and for tumour recurrence.

• Effects of VEGF loading on scaffold-confined vascularization.

  Authors: Daniel Lindhorst, Frank Tavassol, Constantin von See, Paul Schumann, Matthias W Laschke, Yves Harder, Kai-Hendrik Bormann, Harald Essig, Horst Kokemüller, Andreas Kampmann, André Voss, Rolf Mülhaupt, Michael D Menger, Nils-Claudius Gellrich, Martin Rücker

  Journal of biomedical materials research. Part A. 12/2010; 95(3):783-92.

  Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß-tricalcium-phosphate (ß-TCP) and porous poly(L-lactide-co-glycolide)Adequate vascularization of tissue-engineered constructs remains a major challenge in bone grafting. In view of this, we loaded ß-tricalcium-phosphate (ß-TCP) and porous poly(L-lactide-co-glycolide) (PLGA) scaffolds via collagen coating with vascular endothelial growth factor (VEGF) and studied whether the VEGF loading improves scaffold angiogenesis and vascularization. Dorsal skinfold chambers were implanted into 48 balb/c mice, which were assigned to 6 groups (n = 8 each). Uncoated (controls), collagen-coated, and additionally VEGF-loaded PLGA and ß-TCP scaffolds were inserted into the chambers. Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed repeatedly during a 14-day observation period using intravital fluorescence microscopy. Furthermore, VEGF release from PLGA und ß-TCP scaffolds was studied by ELISA. Micromorphology was studied from histological specimens. Unloaded ß-TCP scaffolds showed an accelerated and increased angiogenic response when compared with unloaded PLGA scaffolds. In vitro, PLGA released significantly higher amounts of VEGF compared with ß-TCP at the first two days resulting in a rapid drop of the released amount at the following days up to day 7 where the VEGF release was negligible. Nonetheless, in vivo VEGF loading increased neovascularization, especially in ß-TCP scaffolds. This increased vascularization was associated with a temporary leukocytic response with pronounced leukocyte-endothelial cell interaction at days 3 and 6. Histology revealed adequate host tissue response and engraftment of both ß-TCP and PLGA scaffolds. Our study demonstrates that ß-TCP scaffolds offer more suitable conditions for vascularization than PLGA scaffolds, in particular if they are loaded with VEGF.

• Micro-computed tomography and histologic evaluation of the interface of hydrogel expander and underlying bone: influence of pressure distributors on bone resorption.

  Authors: Constantin von See, Martin Rücker, Paul Schumann, Franziska Goetz, Patrick Wefstaedt, Ingo Nolte, Nina von der Hoeh, Andrea Meyer-Lindenberg, Frank Tavassol, Nils-Claudius Gellrich

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 09/2010; 68(9):2179-84.

  Tissue expanders lead to changes in the underlying bone and can cause bone resorption. We investigated whether the insertion of mechanical devices that distribute the load on the bone can influenceTissue expanders lead to changes in the underlying bone and can cause bone resorption. We investigated whether the insertion of mechanical devices that distribute the load on the bone can influence these effects. A total of 28 Lewis rats were assigned to 1 of 4 groups. Hydrogel expanders were placed subcutaneously either directly on the calvaria, on titanium mesh, or on a titanium plate. The fourth group of rats served as the controls. The bone quality and thickness were assessed beneath, and at the periphery of, the expanders using micro-computed tomography and histologic examination. Micro-computed tomography images were obtained before and 21 days after insertion. The images revealed a significant decrease in hydroxyapatite density beneath the expanders in the group with only expanders. This decrease was reduced with the use of titanium mesh and completely prevented with the use of titanium plates. Histologic examination revealed a significant decrease in bone density and marked lacunae beneath the hydrogel expanders in the group with only expanders. In contrast, the titanium mesh decreased the size of the lacunae, and the titanium plates completely prevented both the formation of lacunae and the decrease in bone thickness. The bone resorption caused by hydrogel expanders can be diminished using titanium mesh and completely prevented by the insertion of a titanium plate.

• Accelerated angiogenic host tissue response to poly(L-lactide-co-glycolide) scaffolds by vitalization with osteoblast-like cells.

  Authors: Frank Tavassol, Paul Schumann, Daniel Lindhorst, Branko Sinikovic, André Voss, Constantin von See, Andreas Kampmann, Kai-Hendrik Bormann, Carlos Carvalho, Rolf Mülhaupt, Yves Harder, Matthias W Laschke, Michael D Menger, Nils-Claudius Gellrich, Martin Rücker

  Tissue engineering. Part A. 02/2010; 16(7):2265-79.

  Bone substitutes should ideally promote rapid vascularization, which could be accelerated if these substitutes were vitalized by autologous cells. Although adequate engraftment of porousBone substitutes should ideally promote rapid vascularization, which could be accelerated if these substitutes were vitalized by autologous cells. Although adequate engraftment of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds has been demonstrated in the past, it has not yet been investigated how vascularization is influenced by vitalization or, more precisely, by seeding PLGA scaffolds with osteoblast-like cells (OLCs). For this reason, we conducted an in vivo study to assess host angiogenic and inflammatory responses after the implantation of PLGA scaffolds vitalized with isogeneic OLCs. OLCs were seeded on collagen-coated PLGA scaffolds that were implanted into dorsal skinfold chambers in BALB/c mice (n = 8). Two further groups of animals received either collagen-coated (n = 8) or uncoated PLGA scaffolds (n = 8). Animals that received chambers without implants served as controls (n = 8). Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed for 14 days using intravital fluorescence microscopy. PLGA scaffolds with and without OLCs showed a temporary increase in leukocyte recruitment. At day 3 after implantation, a marked angiogenic host tissue response was observed in close vicinity of all scaffolds studied. At days 6 and 10, the angiogenic response was significantly higher (p < 0.05) in PLGA scaffolds vitalized with OLCs than in uncoated or collagen-coated PLGA scaffolds. The majority of OLCs, however, died within 14 days after implantation. Our study demonstrates that PLGA scaffold vitalization with OLCs accelerates the angiogenic response in the surrounding host tissue. Bone substitutes created by tissue engineering may thus be superior to nonvitalized substitutes although the seeded cells do not survive for long periods.

• Forensic imaging of projectiles using cone-beam computed tomography.

  Authors: Constantin von See, Kai-Hendrik Bormann, Paul Schumann, Friedrich Goetz, Nils-Claudius Gellrich, Martin Rücker

  Forensic science international. 07/2009;

  In patients with gunshot injuries, it is easy to detect a projectile within the body due to the high-density of the object, but artefacts make it difficult to obtain information about the deformationIn patients with gunshot injuries, it is easy to detect a projectile within the body due to the high-density of the object, but artefacts make it difficult to obtain information about the deformation and the exact location of the projectile in surrounding tissues. Cone-beam computed tomography (CBCT) is a new radiological imaging modality that allows radio-opaque objects to be localised and assessed in three dimensions. The full potential of the use of CBCT in forensic medicine has not yet been explored. In this study, three different modern projectiles were fired into the heads of pig cadavers (n=6) under standardised conditions. Tissue destruction and the location of the projectiles were analysed separately using CBCT and multi-slice computed tomography (MDCT). The projectiles had the same kinetic energy but showed considerable differences in deformation behaviour. Within the study groups, tissue destruction was reproducible. CBCT is less severely affected by metallic artefacts than MDCT. Therefore CBCT is superior in visualising bone destruction in the immediate vicinity of the projectile and projectile deformation, whereas MDCT allows soft tissue to be evaluated in more detail. CBCT is an improved diagnostic tool for the evaluation of gunshot injuries. In particular, it is superior to MDCT in detecting structural hard-tissue damage in the immediate vicinity of high-density metal projectiles and in identifying the precise location of a projectile in the body.

• Osseous alterations at the interface of hydrogel expanders and underlying bone.

  Authors: Constantin Stuehmer, Martin Rücker, Paul Schumann, Kai-Hendrik Bormann, Yves Harder, Branko Sinikovic, Nils-Claudius Gellrich

  Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 03/2009;

  INTRODUCTION: In plastic and reconstructive surgery, self-activating hydrogel expanders are used to augment soft-tissue space. The purpose of this study was to investigate the morphological responseINTRODUCTION: In plastic and reconstructive surgery, self-activating hydrogel expanders are used to augment soft-tissue space. The purpose of this study was to investigate the morphological response of underlying bone to the constant pressure exerted by a hydrogel expander. METHODS: Eighteen Lewis rats were randomly divided into three groups. In group 1, a hydrogel expander was placed subperiosteally directly onto the calvaria of the rats. In group 2, the expander and the underlying bone were separated by a polydioxanone (PDS) foil. Group 3 animals served as controls. Before and 14 days after the insertion of the expanders, micro-computed tomography (CT) images were obtained and fused. We analysed hydroxyapatite density beneath and at the periphery of the expander and performed a histomorphometric bone analysis. RESULTS: Whereas there were no significant differences (p<0.05) (groups 1 and 2) in bone density at the periphery of the expanders between the study groups, a significant decrease in hydroxyapatite density beneath the expanders was observed in those animals in which the devices were placed directly onto the calvaria (group 1). Whereas bone thickness was unaffected at the periphery of the expanders in all groups, it was significantly decreased beneath the expanders in all implanted animals. A morphological examination revealed resorption lacunae with a diameter of 218.4+/-56mum in those rats in which the expanders had been placed directly onto the calvaria. CONCLUSION: This study shows the direct influence of hydrogel expanders on underlying bone. Whereas bone resorption and connective tissue formation also occur underneath hydrogel expanders, these effects can be avoided if the expander and the underlying bone are separated by PDS foil. The key to success is to ensure the appropriate placement of expanders and thus to avoid bone resorption.

• A new model for chronic in vivo analysis of the periosteal microcirculation

  Authors: Constantin Stuehmer, Paul Schumann, Kai-Hendrik Bormann, Matthias W. Laschke, Michael D. Menger, Nils-Claudius Gellrich, Martin Rücker

  Microvascular Research.

  ObjectiveMicrovascular perfusion is indispensable for the growth and remodulation of membrane bone. Trauma, inflammation and surgical interventions may alter periosteal perfusion. However, there isObjectiveMicrovascular perfusion is indispensable for the growth and remodulation of membrane bone. Trauma, inflammation and surgical interventions may alter periosteal perfusion. However, there is not much known about periosteal perfusion in membrane bones. Therefore, the aim of this study was to establish a new chronic model that permits the repeated in vivo analysis of the microcirculation of periosteum.MethodsA circular skin island with a diameter of 6 mm was excised at the forehead of six Lewis rats. Then a newly developed chamber was implanted, containing a coverglass to protect the periosteum. Intravital microscopy (IVM) enables a quantitative analysis of periosteal microcirculation immediately as well as 3, 5 and 10 days after chamber implantation. At the end of the experiment the calvaria and periosteum were removed for histological examination. Six unoperated Lewis rats served as histological controls.ResultsThe periosteal microcirculation remained stable over 10 days. The implantation of the chamber did not result in any substantial inflammatory response. The functional microvascular density was 131.2 ± 19.3 cm/cm2. The histological examinations revealed a regular anatomical structure of periosteum and bone including an intact interface.ConclusionThe presented model allows for the first time to conduct a repetitive, quantitative in vivo analysis of the periosteal microcirculation in membrane bone. Future studies may thus evaluate novel strategies to influence the periosteal perfusion.

• Consequences of seeded cell type on vascularization of tissue engineering constructs in vivo

  Authors: Paul Schumann, Frank Tavassol, Daniel Lindhorst, Constantin Stuehmer, Kai-Hendrik Bormann, Andreas Kampmann, Rolf Mülhaupt, Matthias W. Laschke, Michael D. Menger, Nils-Claudius Gellrich, Martin Rücker

  Microvascular Research.

  Implantation of tissue engineering constructs is a promising technique to reconstruct injured tissue. However, after implantation the nutrition of the constructs is predominantly restricted toImplantation of tissue engineering constructs is a promising technique to reconstruct injured tissue. However, after implantation the nutrition of the constructs is predominantly restricted to vascularization. Since cells possess distinct angiogenic potency, we herein assessed whether scaffold vitalization with different cell types improves scaffold vascularization. 32 male balb/c mice received a dorsal skinfold chamber. Angiogenesis, microhemodynamics, leukocyte–endothelial cell interaction and microvascular permeability induced in the host tissue after implantation of either collagen coated poly (l-lactide-co-glycolide) (PLGA) scaffolds (group 4), additionally seeded with osteoblast-like cells (OLCs, group 1), bone marrow mesenchymal stem cells (bmMSCs, group 2) or a combination of OLCs and bmMSCs (group 3) were analyzed repetitively over 14 days using intravital fluorescence microscopy. Apart from a weak inflammatory response in all groups, vascularization was found distinctly accelerated in vitalized scaffolds, indicated by a significantly increased microvascular density (day 6, group 1: 202 ± 15 cm/cm2, group 2: 202 ± 12 cm/cm2, group 3: 194 ± 8 cm/cm2), when compared with controls (group 4: 72 ± 5 cm/cm2). This acceleration was independent from the seeded cell type. Immunohistochemistry revealed in vivo VEGF expression in close vicinity to the seeded OLCs and bmMSCs. Therefore, the observed lack of cell type confined differences in the vascularization process suggests that the accelerated vascularization of vitalized scaffolds is VEGF-related rather than dependent on the potential of bmMSCs to differentiate into specific vascular cells.