Engineering Technology Center for Tissue Engineering of xiAn

Fengcheng, China

Engineering Technology Center for Tissue Engineering of xiAn

Fengcheng, China

Time filter

Source Type

Liao L.,PLA Fourth Military Medical University | Yang X.,PLA Fourth Military Medical University | Yang X.,ZunYi Medical College | Su X.,Xi'an Jiaotong University | And 8 more authors.
Cell Death and Disease | Year: 2013

During the process of aging, especially for postmenopausal females, the cell lineage commitment of mesenchymal stem cells (MSCs) shift to adipocyte in bone marrow, resulting in osteoporosis. However, the cell-intrinsic mechanism of this cell lineage commitment switch is poorly understood. As the post-transcription regulation by microRNAs (miRNAs) has a critical role in MSCs differentiation and bone homeostasis, we performed comprehensive miRNAs profiling and found miR-705 and miR-3077-5p were significantly enhanced in MSCs from osteoporosis bone marrow. Both miR-705 and miR-3077-5p acted as inhibitors of MSCs osteoblast differentiation and promoters of adipocyte differentiation, by targeting on the 3′untranslated region (3′UTR) of HOXA10 and RUNX2 mRNA separately. Combined inhibition of miR-705 and miR-3077-5p rescued the cell lineage commitment disorder of MSCs through restoring HOXA10 and RUNX2 protein level. Furthermore, we found excessive TNFα and reactive oxygen species caused by estrogen deficiency led to the upregulation of both miRNAs through NF-κB pathway. In conclusion, our findings showed that redundant miR-705 and miR-3077-5p synergistically mediated the shift of MSCs cell lineage commitment to adipocyte in osteoporosis bone marrow, providing new insight into the etiology of osteoporosis at the post-transcriptional level. Moreover, the rescue of MSCs lineage commitment disorder by regulating miRNAs expression suggested a novel potential therapeutic target for osteoporosis as well as stem cell-mediated regenerative medicine. © 2013 Macmillan Publishers Limited All rights reserved.


Zhang Y.,PLA Fourth Military Medical University | Zhang Y.,Engineering Technology Center for Tissue Engineering of Xian | Luo H.,Engineering Technology Center for Tissue Engineering of Xian | Zhang Z.,PLA Fourth Military Medical University | And 10 more authors.
Biomaterials | Year: 2010

Since synthetic nerve conduits do not exhibit the characteristics of regeneration, they are generally inadequate substitutes for autologous nerve graft in the repair of long peripheral nerve defects. To resolve this problem, in this study, we constructed a nerve regeneration characteristics-containing nerve graft through integrating xenogeneic acellular nerve matrix (ANM) with autologous neural differentiated adipose-derived mesenchymal stem cells (ADSCs). Xenogeneic ANM was processed by a protocol removing cells and myelin sheath completely, meanwhile preserving growth factors and extracellular matrix (ECM) microstructure of natural nerve, such as porous and basal lamina tube. Cytocompatibility and immunocompatibility evaluation revealed that ANM could support cell attachment and proliferation, and did not stimulate vigorous host reject response. After inoculation of neural differentiated ADSCs onto ANM, differentiated cells were observed to align along longitudinal axis of ANM, resembling band of büngner, and persistently express NGF, GDNF, and BDNF. In vivo, neural differentiated ADSCs also presented glial cell characteristics and promote nerve regeneration 7 days post transplantation. We repaired 1. cm Sprague Dawley rat sciatic nerve defects using this nerve graft construction and nerve gap regeneration was indicated by electrophysiology, retrograde labeling and histology analysis. Therefore, we conclude that constructed nerve graft, offering nerve regeneration characteristics, hold great promise to replace autologous in repair peripheral nerve defect. © 2010 Elsevier Ltd.


Chen X.,PLA Fourth Military Medical University | Hu C.,PLA Fourth Military Medical University | Hu C.,Engineering Technology Center for Tissue Engineering of xiAn | Wang G.,PLA Fourth Military Medical University | And 5 more authors.
Cell Death and Disease | Year: 2013

Inflammation can influence multipotency and self-renewal of mesenchymal stem cells (MSCs), resulting in their awakened bone-regeneration ability. Human periodontal ligament tissue-derived MSCs (PDLSCs) have been isolated, and their differentiation potential was found to be defective due to b-catenin signaling indirectly regulated by inflammatory microenvironments. Nuclear factor-κB (NF-κB) is well studied in inflammation by many different groups. The role of NF-κB needs to be studied in PDLSCs, although genetic evidences have recently shown that NF-κB inhibits osteoblastic bone formation in mice. However, the mechanism as to how inflammation leads to the modulation of β-catenin and NF-κB signaling remains unclear. In this study, we investigated b-catenin and NF-κB signaling through regulation of glycogen synthase kinase 3b activity (GSK-3b, which modulates b-catenin and NF-κB signaling) using a specific inhibitor LiCl and a phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002. We identified that NF-κB signaling might be more important for the regulation of osteogenesis in PDLSCs from periodontitis compared with β-catenin. BAY 11-7082 (an inhibitor of NF-κB) could inhibit phosphorylation of p65 and partly rescue the differentiation potential of PDLSCs in inflammation. Our data indicate that NF-κB has a central role in regulating osteogenic differentiation of PDLSCs in inflammatory microenvironments. Given the molecular mechanisms of NF-κB in osteogenic differentiation governed by inflammation, it can be said that NF-κB helps in improving stem cell-mediated inflammatory bone disease therapy. © 2013 Macmillan Publishers Limited All rights reserved.


Yang N.,PLA Fourth Military Medical University | Yang N.,PLA 309th Hospital | Wang G.,PLA Fourth Military Medical University | Hu C.,PLA Fourth Military Medical University | And 14 more authors.
Journal of Bone and Mineral Research | Year: 2013

Inflammatory cytokines, especially tumor necrosis factor α (TNF-α), have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen deficiency-induced osteoporosis, but the mechanism responsible remains poorly understood. MicroRNAs (miRNAs) have been shown to regulate MSC differentiation. Here, we identified a novel mechanism whereby TNF-α, suppressing the functional axis of a key miRNA (miR-21) contributes to estrogen deficiency-induced osteoporosis. In this study, we screened differentially expressed miRNAs in MSCs derived from estrogen deficiency-induced osteoporosis and found miR-21 was significantly downregulated. miR-21 was suppressed by TNF-α during the osteogenesis of MSCs. Furthermore, miR-21 was confirmed to promote the osteoblast differentiation of MSCs by repressing Spry1, which can negatively regulate the osteogenic differentiation of MSCs. Upregulating miR-21 partially rescued TNF-α-impaired osteogenesis of MSCs. Blocking TNF-α ameliorated the inflammatory environment and significantly enhanced bone formation with increased miR-21 expression and suppressed Spry1 expression in ovariectomized (OVX) mice. Our results revealed a novel function for miR-21 and suggested that suppressed miR-21 may contribute to impaired bone formation by elevated TNF-α in estrogen deficiency-induced osteoporosis. This study may indicate a molecular basis for novel therapeutic strategies against osteoporosis and other inflammatory bone diseases. © 2013 American Society for Bone and Mineral Research.


Liu Y.,Chinese PLA General Hospital | Liu Y.,PLA Fourth Military Medical University | Ming L.,PLA Fourth Military Medical University | Ming L.,Engineering Technology Center for Tissue Engineering of Xian | And 12 more authors.
Biomaterials | Year: 2013

Reconstruction of large area bone defect with mechanical integrity to the skeleton is important for patient's rehabilitation. However with the limitation of scaffold material and suitable seed cell sources, the best treating strategy remains to be identified though various tissue engineering methods were reported. In this study, we investigated the feasibility of applying calcined bovine bone (CBB) which was coated by allograft bone marrow mesenchymal stem cells (BMSC)-sheet as a 3D scaffold material in bone repairing tissue engineering. The new scaffold material was implanted into osteoporosis rat cranial bone defects and repairing critical size bone defects (8mm diameter). Data showed that CBB-BMSC-sheet combination had a stronger potential in osteogenic differentiation and mineralized formation both invitro and invivo than CBB-BMSC combination. In invitro study BMSC-sheet had a more feasible characteristic upon bone repairing including richer ECM, larger mineralized area and stronger ALP activity in addition with a significant higher mRNA expression of osteogenic maker such as BMP-2, b-FGF, Col 1a1, OSX and Runx-2 than the control group. In invivo study 3D reconstruction of micro CT, HE staining and bone strength results showed that newly formed bone in CBB-BMSC-sheet group was significant higher than that in CBB-BMSC group at 4, 8 and 12 weeks after transplantation in the aspect of area and volume. What was more, results indicated that allograft BMSC-sheet had survivaled in the scaffold material and participated in the newly formed bone which had the same thickness with surrounding autologous bone tissues after transplantation. Results of our study demonstrated that CBB-BMSC-sheet combination was a promising strategy in healing of large area bone defect in osteoporosis. © 2013 Elsevier Ltd.


Peng H.,PLA Fourth Military Medical University | Ming L.,PLA Fourth Military Medical University | Ming L.,Engineering Technology Center for Tissue Engineering of Xian | Yang R.,PLA Fourth Military Medical University | And 5 more authors.
Biomaterials | Year: 2013

Stem cell transplantation is a kind of attractive and new approach that complements traditional restorative or surgical techniques for the regeneration of injured or pathologically damaged laryngeal tissues. However, the best cell delivery strategy remains to be identified. The objective of this study was to establish a new strategy to the healing of injured vocal fold, using laryngeal mucosa mesenchymal stem cells differentiating into myofibroblasts or fibroblasts and improving the reconstruction microenvironment in the vocal fold injury as a new alternative as seed cells for laryngeal tissue engineering. After isolation and expansion, cells were identified as adherent mesenchymal cells with substantial proliferation potential invitro, and were also characterized by flow cytometry. The differentiation potential of mesenchymal cells was maintained during proliferation as confirmed by culturing for adipogenesis, osteogenesis and chondrocyte. When LM-MSC was transplanted into the injured vocal fold, it has the potent differentiated into myofibroblasts and fibroblasts, which could regulate extracellular matrix, block collagen and the fibronectin rapid increased, inhibit the rapidly decrease of elastic fiber and HA, decrease the microenvironment inflammatory reaction, and prevent the formation of vocal fold scar. © 2013 Elsevier Ltd.


Luo H.,PLA Fourth Military Medical University | Luo H.,Engineering Technology Center for Tissue Engineering of Xian | Lu Y.,PLA Fourth Military Medical University | Lu Y.,Engineering Technology Center for Tissue Engineering of Xian | And 6 more authors.
Biomaterials | Year: 2013

Although acellular corneas have been reported to be a potential substitute for allogeneic cornea transplantation to treat corneal injury, severe corneal injury is hard to repair due to inflammation and neovascularization. The use of the amniotic membrane as a graft in ocular surface reconstruction has become widespread because of the anti-inflammatory and anti-angiogenic properties of amniotic epithelial cells (AECs). Our objective was to construct a tissue-engineered cornea (TEC) composed of an acellular porcine cornea (APC) and AECs to repair severe corneal injury. Corneal cells were completely removed from the prepared APC, and the microstructure, mechanical properties, and stability of a natural porcine cornea (NPC) was maintained. Invitro, MTT and flow cytometry analyses showed that the APC did not negatively affect cell viability and apoptosis. Invivo, corneal pocket and subcutaneous transplantation demonstrated that the APC was incapable of trigging accepted immune response. AECs isolated from the human amniotic membrane have proliferation potential and present healthy morphology before 6 passages. After 7 days of culture on the surface of the APC, the AECs were stratified into 5-6 layers. We found that the AECs reconstituted the basement membrane that had been disrupted by the decellularization process. ELISA results showed that after culturing the TEC, the culture medium contained anti-inflammatory and anti-angiogenic growth factors, such as MIF, IL6, Fas-L, and PDEF. Finally, the results of lamellar keratoplasty to treat an alkali burn showed that the transplanted TEC was transparent and completely inoculated into the host cornea. However, the transplanted APC was degraded due to host rejection. Therefore, we conclude that a TEC composed of AECs and an APC holds great potential for the repair of severe corneal injury. © 2013 Elsevier Ltd.


Luo H.,Engineering Technology Center for Tissue Engineering of Xian | Zhang Y.,PLA Fourth Military Medical University | Zhang Y.,Engineering Technology Center for Tissue Engineering of Xian | Zhang Z.,Engineering Technology Center for Tissue Engineering of Xian | Jin Y.,PLA Fourth Military Medical University
Biomaterials | Year: 2012

Our previous report demonstrated that autologous adipose-derived mesenchymal stem cells (ADSCs) combined with xenogeneic acellular nerve matrix (XANM) can support the regeneration of defective nerves. Although ADSCs had the potential to replace Schwann cells in engineered-tissue nerves, apoptosis easily obstructed the ability to treat serious nerve injury in the host, such as a >50-mm-long nerve defect. In the present study, we found that, in combination with transforming growth factor β1 (TGFβ1), an ADSCs-XANM graft was sufficient to support the regeneration of a 50-mm sciatic nerve defect, which was not achieved using an ADSCs-XANM graft alone. Based on this finding, we further investigated how TGFβ1 coordinated with ADSCs to enhance nerve regeneration. In vitro, cell culture experiments demonstrated that TGFβ1 did not have a direct effect on ADSC proliferation, apoptosis, the cell cycle, or neural differentiation. The expression of VEGF, however, was significantly increased in ADSCs cultured with TGFβ1. In vivo, fluorescence labeling experiments demonstrated that the survival of transplanted ADSCs inoculated with XANM-TGFβ1 was higher than with XANM. Further study showed that TGFβ1 was capable of impairing the host immune response that was trigged by transplanted XANM. Additionally, we discovered that XANM-ADSCs in immunodeficient mice had apoptosis rates similar to XANM-ADSCs-TGFβ1 over a short time course (7 days). Once we blocked VEGF with a neutralizing antibody, the protective effect of TGFβ1 was impaired over a long time course (28 days). These results suggested that TGFβ1 was capable of enhancing the regenerative capacity of an XANM-ADSCs graft, mainly by protecting transplanted ADSCs from apoptosis. This effect was achieved in part through decreasing inflammation and promoting VEGF-dependent angiogenesis. © 2012 Elsevier Ltd.


Liu S.,PLA Fourth Military Medical University | Zhang H.,PLA Fourth Military Medical University | Zhang X.,PLA Fourth Military Medical University | Lu W.,PLA Fourth Military Medical University | And 9 more authors.
Tissue Engineering - Part A | Year: 2011

Slow vascularization rate is considered one of the main drawbacks of scaffolds used in wound healing. Several efforts, including cellular and acellular technologies, have been made to induce vascular growth in scaffolds. However, thus far, there is no established technology for inducing vascular growth. The aim of this study was to promote the vascularization capacities of scaffolds by seeding adipose-derived stem cells (ADSCs) on them and to compare the vascularization capacities of different scaffolds seeded with ADSCs. Two kinds of extracellular matrix scaffolds (small intestinal submucosa [SIS] and acellular dermal matrix [ADM]) and a kind of composite scaffold (collagen-chondroitin sulfate-hyaluronic acid [Co-CS-HA]) were selected. Subcutaneous implantation analysis showed that the vascularization capacity of SIS and ADM was greater than that of Co-CS-HA. ADSCs seeded in SIS and ADM secreted greater amounts of vascular endothelial growth factor than those seeded in Co-CS-HA. In a murine skin injury model, ADSC-seeded scaffolds enhanced the angiogenesis and wound healing rate compared with the nonseeded scaffolds. Moreover, ADSC-SIS and ADSC-ADM had greater vascularization capacity than that of ADSC-Co-CS-HA. Taken together, these results suggest that ADSCs could be used as a cell source to promote the vascularization capacities of scaffolds. The vascularization capacities of ADSC-seeded scaffolds were influenced by both the vascularization capacities of the scaffolds themselves and their effects on the angiogenic potential of ADSCs; the combination of extracellular matrix scaffolds and ADSCs exhibited synergistic angiogenesis promoting effects. © Mary Ann Liebert, Inc. 2011.


Shang F.,PLA Fourth Military Medical University | Ming L.,PLA Fourth Military Medical University | Ming L.,Engineering Technology Center for Tissue Engineering of Xian | Ming L.,Institute for Tissue Engineering and Regenerative Medicine Research of Xian | And 6 more authors.
Biomaterials | Year: 2014

Treatment of weight-bearing bones fractures with defects is critical for patients with osteoporosis's rehabilitation. Although various tissue engineering methods were reported, the best treating strategy for tissue engineering remains to be identified as the limitation of enhancing the ability of the osteogenetic differentiation potential of seed cell is one of the cardinal issues to be solved. The objective of this study is to investigate the feasibility of applying licochalcone-A (L-A) and bone marrow mesenchymal stem cells (BMSC)-aggregate in bone repairing tissue engineering and further study the biological effects of L-A on the cell aggregate formation and osteogenic properties. 80 female SpragueDawley rats underwent bilateral ovariectomy were made with a 3.5mm femurs bone defects without any fixation. These rats were then randomly assigned to five different treatment groups: (1) empty defect (n=16), (2) CA-LA (n=16), (3) CA-N (n=16), (4) CA-L (n=16), (5) CA-S (n=16) and 16 female SD rats were treated as a control. Data showed that L-A administrated cell aggregate had a stronger osteogenic differentiation and mineralized formation potential than non-administrated group both invitro and invivo. For invitro study, L-A administrated group had a more significant expression of ECM, osteogenic associated maker in addition with more mineralized area and higher ALP activity compared with the control group. For invivo study, 3D reconstruction of micro-CT, HE staining and bone strength results showed that newly formed bone in groups administrated by L-A was significant higher than that in Sham group at 2, 4, 8 and 12 weeks after transplantation, especially for groups which was systematically injected with L-A at 8 weeks. Results of our study demonstrated that LA could positively affect cell behavior in cell-aggregate engineering and could be a promising strategy in treating osteoporotic weight-bearing bones fractures with defects. © 2014 Elsevier Ltd.

Loading Engineering Technology Center for Tissue Engineering of xiAn collaborators
Loading Engineering Technology Center for Tissue Engineering of xiAn collaborators