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ABSTRACT: The administration of human adipose-derived stromal cells (hASCs) enhances skin wound healing. However, poor survival of hASCs that are administered to avascular wound regions may limit the therapeutic efficacy of the hASCs. The aim of this study was to determine whether the co-administration of platelet-rich plasma (PRP) and hASCs enhanced the skin wound-healing efficacy of hASCs. Skin regeneration was examined in skin wounds of athymic mice that were treated with nothing, hASCs, PRP, or both hASCs and PRP. Coadministration of PRP and hASCs resulted in better skin regeneration than hASC administration alone in part by significantly improving the proliferation of administered hASCs, angiogenic growth factor secretion of the hASCs and surrounding mouse host cells in the wound areas, and promoting neovascularization in the wound beds.
Cell Transplantation 10/2012; · 5.13 Impact Factor
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ABSTRACT: BACKGROUND: Skin flap survival is a major challenge in reconstructive plastic surgery. Here, we examined the effect of sustained delivery of fibroblast growth factor 2 (FGF2) using heparin-conjugated fibrin (HCF) on skin flap survival in rats. METHODS: Rats with a skin flap received either phosphate-buffered saline/FGF2 or HCF/FGF2 in the recipient bed. For the no-treatment group, a random skin flap was sutured on the back without any treatment. Seven days after surgery, angiogenesis in the skin flap was evaluated by using Visitrak system and conventional healing quality scoring method. The efficacy of HCF/FGF2 in skin flap survival was evaluated by comparing the results from different groups. RESULTS: The necrotic area of the skin flap significantly decreased in the HCF/FGF2 group as compared with the other groups. CONCLUSION: The sustained delivery of FGF2 using HCF has a therapeutic potential to improve skin flap survival.
ANZ Journal of Surgery 09/2012; · 1.25 Impact Factor
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ABSTRACT: In this article, we examined the feasibility of using 3,4-dihydroxy-L-phenylalanine (DOPA) as a cell adhesion molecule in serum-free cultures of anchorage-dependent mammalian cells. DOPA is a critical, functional element in mussel adhesive proteins and is known to bind strongly to various natural or synthetic materials. DOPA coating on culture plates was confirmed using X-ray photoelectron spectroscopy and energy-dispersive spectroscopy. Human dermal fibroblasts (HDFs) were cultured on DOPA-coated, fibronectin-coated, or no material-coated culture plates in serum-free medium. HDFs cultured on DOPA showed the highest cell adhesion ratio, spreading, and viability but the lowest apoptotic activity. Therefore, DOPA may be a useful cell-adhesion molecule for serum-free culture.
Biotechnology Progress 05/2012; 28(4):1055-60. · 2.34 Impact Factor
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ABSTRACT: Stem cell transplantation can induce neovascularization. Regenerated blood vessels should remain stable for a long-term period in order to function as new blood vessels in ischemic tissues. Here we show that local delivery of FGF2 enhances the long-term (12weeks) angiogenic efficacy of human adipose-derived stem cells (hADSCs) implanted into mouse ischemic hindlimbs. Following transplantation of hADSCs into ischemic hindlimbs of mice, hADSC viability was significantly higher in the hADSC+FGF2 group at 4 and 12weeks post-transplantation than in the hADSC only group. Furthermore, hADSCs produced higher levels of angiogenic growth factors (i.e., fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor, and platelet-derived growth factor) at both time points. As a result, the density of arterioles in the ischemic hindlimb muscle was significantly higher in the hADSC+FGF2 group than in either hADSC or FGF2 only group at both time points. The number of arterioles with larger diameters was significantly greater in the hADSC+FGF2 group than in the other groups at 12weeks, and increased in the hADSC+FGF2 group as the time period increased from 4weeks to 12weeks post-transplantation. This suggests that FGF2 delivery to hADSC transplantation sites enhances long-term angiogenic efficacy of hADSCs transplanted into ischemic tissues.
Microvascular Research 04/2012; 84(1):1-8. · 2.83 Impact Factor
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ABSTRACT: Bone morphogenetic protein-2 (BMP-2) can induce bone generation in vivo. Although many studies have demonstrated an increased quantity of regenerated bone after the delivery of BMP-2 using various carriers, little is known about the effect of the carrier type on the quality of the regenerated bone. In this study, we compared the quality of regenerated bone when BMP-2 was delivered with either β-tricalcium phosphate (β-TCP) or heparin-conjugated fibrin (HCF), both of which are shown to be excellent carriers for BMP-2. The profile of the release of BMP-2 was not significantly different between the delivery carriers. However, the alkaline phosphate activity of cultured osteoblasts was significantly higher when BMP-2 was delivered using HCF than when BMP-2 was delivered using β-TCP. To evaluate the quality of the regenerated bone, both types of BMP-2 carriers were implanted into critical-sized calvarial defects in mice. Eight weeks after implantation, the regenerated bone was examined by histomorphometry. Importantly, the treatment using HCF + BMP-2 and β-TCP + BMP-2 resulted in similar bone formation areas. However, the treatment using HCF + BMP-2 resulted in significantly higher bone density than the treatment using β-TCP + BMP-2. This study shows that a BMP-2 delivery carrier can modulate the quality of bone regenerated via BMP-2 delivery.
Artificial Organs 02/2012; 36(7):642-7. · 2.00 Impact Factor
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ABSTRACT: Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin- conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher alkaline phosphatase activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle.
Experimental and Molecular Medicine 02/2012; 44(5):350-5. · 2.48 Impact Factor
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ABSTRACT: To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period.
A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks.
Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery.
Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.
Clinics in orthopedic surgery 12/2011; 3(4):325-31.
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ABSTRACT: Various new delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2) have been introduced to improve its efficacy in osteogenesis. Of these, we have previously developed heparin-conjugated PLGA nanospheres (HCPN) as a long-term delivery system for BMP-2. In vitro studies have shown that the BMP-2 long-term delivery system enhances the level of bone formation. However, the long-term effects of BMP-2 on spinal fusion have not been assessed. Therefore, we now tested the hypothesis that the long-term delivery of BMP-2 using HCPN improves spinal fusion compared to short-term delivery in a rabbit fusion model.
24 adult New Zealand White rabbits underwent posterolateral fusion (6 animals in 4 groups). The autograft group received an autologous iliac chip bone graft as a positive control. The BMP-2-PN group received rhBMP-2 (20 μg per implant) and PLGA nanospheres (PN) suspended in fibrin gel, and served as a short-term release group. The HCPN group received HCPN suspended in fibrin gel without BMP-2 as a negative control. The BMP-2-HCPN group received rhBMP-2 (20 μg per implant)-bound HCPN suspended in fibrin gel and served as a long-term release group. All animals were killed 12 weeks after surgery. Manual palpation, axial tensile tests, radiography, and histological evaluations were then performed.
The spinal fusion rate and Young's modulus of the fusion mass were better in the BMP-2 long-term delivery group than in the short-term delivery group at an equivalent dose. However, the outcome of the long-term delivery was inferior to that of the autograft group.
The HCPN system showed potential as an effective carrier that might improve the osteogenic efficacy of BMP-2 for spinal fusion.
Acta Orthopaedica 11/2011; 82(6):756-60. · 2.17 Impact Factor
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ABSTRACT: For bone regeneration applications, scaffolds made from a composite of a biodegradable polymer and ceramic have advantages over scaffolds made from only one component (biodegradable polymer or ceramic alone). In this study, a simple and rapid method was developed to induce hydroxyapatite (HA) nanoparticle adsorption on polyglycolic acid (PGA) scaffold surfaces. PGA meshes were coated with HA nanoparticles by immersing the scaffolds in a buffer solution containing 3,4-dihydroxyphenylalanine (DOPA), a critical, functional element in mussel adhesive protein known to strongly bind to various materials. Substantial HA coating on PGA scaffolds was achieved within 24 hours of immersion, as determined according to selective staining of ceramic particles, scanning electron microscopy, X-ray photoelectron spectroscopy, and energy-dispersive spectroscopy. To evaluate the osteoconduction efficacy of the scaffolds in vivo, PGA scaffolds, DOPA-coated PGA scaffolds, PGA scaffolds immersed in HA solution, and HA- and DOPA-coated PGA (HA-DOPA-PGA) scaffolds were implanted in critical-sized defects in mouse skulls for 8 weeks. Micro-computed tomography and histological analyses showed that bone regeneration in vivo was far more extensive on HA-DOPA-PGA scaffolds than on the other scaffolds. DOPA offers an efficient and simple method of HA coating on polymer scaffolds. HA-polymer composite scaffolds fabricated using this method could be useful as bone graft.
Tissue Engineering Part C Methods 11/2011; 18(4):245-51. · 4.64 Impact Factor
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ABSTRACT: Despite the great potential of cell therapy for ischemic disease, poor cell survival after engraftment in ischemic tissue limits its efficacy. Here we tested a hypothesis that three-dimensionally grafted human umbilical vein endothelial cell (HUVEC) spheroids would exhibit improved angiogenic efficacy following transplantation into mouse ischemic limbs compared with HUVECs prepared by conventional two-dimensional monolayer culture. One day after surgical induction of hindlimb ischemia in athymic mice, HUVECs cultured in monolayer or HUVEC spheroids were transplanted intramuscularly into ischemic limbs. Four weeks after the treatment, in the spheroid HUVEC transplantation group, we observed increased hypoxia-inducible factor-1α expression, decreased apoptosis, and increased HUVEC survival in the ischemic tissue compared with the monolayer HUVEC transplantation group. Transplantation of HUVEC spheroids also resulted in enhanced and prolonged secretion of paracrine factors as well as enhanced expression of factors involved in the recruitment of circulating angiogenic progenitor cells. In summary, transplantation of HUVECs as spheroids enhanced cell survival, increased paracrine factor secretion, and showed a potential as a therapeutic method to treat ischemic tissue damages by promoting angiogenesis.
Tissue Engineering Part A 09/2011; 18(3-4):310-9. · 4.64 Impact Factor
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ABSTRACT: Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. Clinically utilized BMP-2 uses a type-I collagen scaffold as a carrier. Here we hypothesized that an apatite coating on a type-I collagen scaffold would prolong the BMP-2 release period and enhance bone regeneration in calvarial defects in mice. Apatite coating was achieved by incubating collagen scaffolds in simulated body fluid. BMP-2 release kinetics and bioactivity were evaluated by enzyme-linked immunosorbent assay and alkaline phosphatase activity measurement of cultured osteoblasts. Computed tomography and histomorphometry were performed eight weeks after various doses of BMP-2 were delivered to mouse calvarial defects using either non-modified or apatite-coated collagen scaffolds. Apatite-coated collagen scaffolds released 91.8±11.5% of the loaded BMP-2 over 13 days in vitro, whereas non-modified collagen scaffolds released 98.3±2.2% over the initial one day. The in vivo study showed that BMP-2 delivery with apatite-coated collagen scaffolds resulted in a significantly greater bone formation area and higher bone density than that with non-modified collagen scaffolds. This study suggests that simple apatite coating on collagen scaffolds can enhance the bone regeneration efficacy of BMP-2 released from collagen scaffolds.
Journal of Biomaterials Science Polymer Edition 08/2011; · 1.69 Impact Factor
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ABSTRACT: Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.
Experimental and Molecular Medicine 08/2011; 43(11):622-9. · 2.48 Impact Factor
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ABSTRACT: Bone marrow mononuclear cells (BMMNCs) can be used to treat patients with myocardial infarction, since BMMNCs can differentiate in vitro toward cardiomyogenic lineages when treated with transforming growth factor-β1 (TGF-β1). However, the in vitro cardiomyogenic differentiation culture process is costly and laborious, and the patients should wait during the culture period. In this study, we hypothesize that BMMNCs implanted in cardiomyogenically undifferentiated state to myocardial infarction site would differentiate cardiomyogenically in situ when exogenous TGF-β1 is delivered to the cell implantation site. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) suspended in fibrin gel were used as a TGF-β1 delivery system. BMMNCs were labeled with a green fluorescent dye (PKH67) and implanted into the infarction border zone of rat myocardium using fibrin gel containing HCPNs and TGF-β1. BMMNC implantation using fibrin gel and HCPNs without TGF-β1 served as a control. Four weeks after implantation, the expression of cardiomyogenic marker proteins by the implanted BMMNCs was dramatically greater in the TGF-β1 delivery group than in the control group. This method can significantly improve the stem cell therapy technology for myocardial regeneration, since it can remove in vitro cell culture step for cardiomyogenic differentiation prior to cell implantation.
Cell Transplantation 06/2011; 21(1):299-312. · 5.13 Impact Factor
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ABSTRACT: Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. BMP-2 is clinically used for spine fusion and bone fracture healing. Commercially available BMP-2 uses a type I collagen scaffold as a carrier, but it only releases BMP-2 for a short period of time, which may release the bone formation efficacy. In the present study, we hypothesize that apatite coating of a collagen scaffold increases the release period as well as the osteogenic efficacy of BMP-2. Apatite coating was achieved by incubating collagen scaffolds in simulated body fluids (SBFs). Apatite coating on collagen scaffolds was confirmed by X-ray diffraction, electron spectroscopy for chemical analysis, attenuated total reflectance-Fourier transform infrared spectroscopy, and scanning electron microscopy. The rate and period of BMP-2 release from apatite-coated collagen scaffolds varied depending on the concentration of SBFs used. The 5× and 10× SBF apatite-coated collagen scaffolds released 91.8%±11.5% and 82.2%±13.1% of their loaded BMP-2 over 13 days in vitro, respectively, whereas noncoated collagen scaffold released 98.3%±2.2% over the initial one day. BMP-2 released from apatite-coated collagen scaffold significantly increased the alkaline phosphatase activity of cultured osteoblasts, compared with BMP-2 released from noncoated collagen scaffold. Computed tomography and histomorphometry showed that BMP-2 delivery using apatite-coated collagen scaffolds resulted in 2.5-fold higher bone formation volume and 4.0-fold higher bone formation area than BMP-2 delivery using noncoated collagen scaffolds. This study shows that simple apatite coating of a collagen scaffold results in a BMP-2 carrier that renders long-term release of BMP-2 and dramatically enhances osteogenic efficacy.
Tissue Engineering Part A 04/2011; 17(17-18):2153-64. · 4.64 Impact Factor
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ABSTRACT: Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor engraftment in vivo. Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1α and hypoxia-inducible factor-1α), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell-matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification.
Biomaterials 04/2011; 32(11):2734-47. · 7.40 Impact Factor
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ABSTRACT: Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.
Tissue Engineering Part A 03/2011; 17(13-14):1809-18. · 4.64 Impact Factor
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ABSTRACT: Recent studies have demonstrated the existence of osteoblast progenitor cells in circulating blood. Here we show that local delivery of bone morphogenetic protein-2 (BMP-2) to cell transplantation sites induces in situ osteogenic differentiation of transplanted human peripheral blood mononuclear cells (PBMNCs) and enhances in vivo bone formation mediated by PBMNC transplantation. Human PBMNCs were seeded on scaffolds with or without BMP-2 and implanted subcutaneously into athymic mice. Nonseeded scaffolds with BMP-2 were also implanted. Eight weeks later, radiographic and histological analyses showed that the PBMNC + BMP-2 group had undergone much more extensive bone formation than either the PBMNC group or BMP-2 group. Only the PBMNC + BMP-2 group expressed human Cbfa1, osteonectin, and osteocalcin, suggesting in situ osteogenic differentiation of and bone formation by transplanted human PBMNCs, while the other groups did not express these genes. This study provides a method to enhance human PBMNC transplantation-mediated bone formation.
Cell Transplantation 03/2011; 20(9):1445-52. · 5.13 Impact Factor
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ABSTRACT: Bone morphogenetic protein-2 (BMP-2) induces bone regeneration in a dose-dependent manner, with higher doses of BMP-2 inducing greater bone formation. Previously, we showed that long-term delivery of BMP-2 provides better ectopic bone formation than short-term delivery of an equivalent dose. In the present study, we investigated the efficacy of orthotopic bone formation over a range of BMP-2 doses, using different delivery modes. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres suspended in fibrin gel were used as a long-term delivery system, and fibrin gel was used as a short-term delivery system. Different doses of BMP-2 were delivered to mouse calvarial defects using either long-term or short-term delivery systems. Eight weeks after treatment, bone regeneration was evaluated by histomorphometry. For both delivery systems, bone regeneration increased as the BMP-2 dose increased up to 1 µg and did not increase beyond this dose. Importantly, at BMP-2 doses higher than 1 µg, long-term delivery resulted in much greater bone formation than short-term delivery. This study shows that long-term delivery of BMP-2 is more effective at enhancing orthotopic bone formation than short-term delivery over a range of doses.
Artificial Organs 12/2010; 34(12):1150-3. · 2.00 Impact Factor
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ABSTRACT: Implantation of chondrocytes isolated from patients and expanded in number in vitro is being used to treat patients with cartilage injuries. However, chondrocytes de-differentiate during culture with several passages, and cartilage regenerated by implantation of de-differentiated chondrocytes may be suboptimal. Here, we show that a spinner-flask culture system induces formation of chondrocyte aggregates and redifferentiate de-differentiated chondrocytes. Spinner-flask cultures induced the aggregate formation of chondrocytes with passage 1 or 4. Importantly, spinner-flask cultures induced redifferentiation of the de-differentiated chondrocytes, as type I collagen expression was significantly lower and type II collagen expression was significantly higher in spinner flask-cultured chondrocytes than in monolayer-cultured chondrocytes. This system is easily scalable and could be feasible for clinical setting.
Biotechnology Letters 12/2010; 33(4):829-36. · 1.68 Impact Factor
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ABSTRACT: Fibroblast growth factor 2 (FGF2) stimulates skin wound healing but does long-term delivery of FGF2 enhance skin regeneration compared to short-term delivery? Heparin-conjugated fibrin (HCF) was used as a vehicle for long-term delivery of FGF2. Fibrin, HCF, FGF2-loaded fibrin, and FGF2-loaded HCF were implanted into full-thickness skin defects of mice. The neoepidermis thickness was significantly larger in the FGF2-loaded HCF group than in the other groups, except for the FGF2-loaded fibrin group. Suprabasal cytokeratin differentiation in squamous neoepithelium was greatest in the FGF2-loaded HCF group. The enhanced skin regeneration accompanying the long-term delivery of FGF2 could be mediated, at least partially, by enhanced neovascularization and cell proliferation in the neodermis.
Biotechnology Letters 12/2010; 33(4):845-51. · 1.68 Impact Factor
