Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold.

BACKGROUND: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. METHOD: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. RESULTS: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. CONCLUSION: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

Clinical Outcomes Between Atrophic and Nonatrophic Mandibular Fracture in Elderly Patients.

The number of elderly patients with mandibular fracture is rapidly increasing. To improve outcome, it is important to understand the age-related characteristics of mandibular fracture. Thus, the aim of this study is to analyze the impact of atrophic change on mandibular fracture in elderly patients. The retrospective study was conducted in patients aged ≥65 years old, who underwent surgery for the treatment of mandibular fracture in our hospital from March 2006 until March 2015. Patient characteristics, such as age and gender, causes of injury, anatomic location of fracture, height of mandibular body, extent of atrophy, location of surgical sites, postoperative outcomes, and the follow-up period, were examined. Descriptive statistics were compared between atrophic and nonatrophic mandibles. The patients included 17 males and 12 females and the mean age was 71.9 years old. The average follow-up period was 6.06 months. Regarding occlusion and complications, there were no statistical differences between the atrophic and nonatrophic mandibular fractures. As major complications, nonunion occurred in 2 patients and malunion in 1 patient. There was no mortality associated with anesthesia or surgery. Atrophic and nonatrophic mandibular fractures in elderly patients can be treated successfully with surgery. There was no significant difference with respect to major complications between patients with atrophic and nonatrophic mandibular fractures.

Intrinsic and extrinsic mechanical properties related to the differentiation of mesenchymal stem cells.

Diverse intrinsic and extrinsic mechanical factors have a strong influence on the regulation of stem cell fate. In this work, we examined recent literature on the effects of mechanical environments on stem cells, especially on differentiation of mesenchymal stem cells (MSCs). We provide a brief review of intrinsic mechanical properties of single MSC and examined the correlation between the intrinsic mechanical property of MSC and the differentiation ability. The effects of extrinsic mechanical factors relevant to the differentiation of MSCs were considered separately. The effect of nanostructure and elasticity of the matrix on the differentiation of MSCs were summarized. Finally, we consider how the extrinsic mechanical properties transfer to MSCs and then how the effects on the intrinsic mechanical properties affect stem cell differentiation.

Development of Porous Beads to Provide Regulated BMP-2 Stimulation for Varying Durations: In Vitro and In Vivo Studies for Bone Regeneration.

It is commonly accepted that the sustained release of bone morphogenetic protein-2 (BMP-2) can enhance bone regeneration and minimize its safety issues. However, little is known regarding the appropriate duration of BMP-2 stimulation for sufficient osteogenic differentiation and new bone formation because of the short half-life of BMP-2 in the physiological environment and the lack of a well-defined delivery matrix that can regulate the release period of BMP-2. In this study, we prepared porous poly(lactic-co-glycolic acid) (PLGA) beads with different surface pore sizes that can regulate the release period of BMP-2 (i.e., 7, 17, and 30 days) while providing the BMP-2 concentration required for bone regeneration. Our findings in both in vitro cell culture and in vivo animal studies using these BMP-2-loaded beads demonstrate that release of BMP-2 within 7 days affects only the initial differentiation of human periosteum-derived cells (hPDCs) and does not significantly enhance their subsequent differentiation into mature functional cells. However, extending the duration of BMP-2 stimulation over 17 days can provide a suitable environment for osteogenic differentiation of hPDCs and new bone formation.

Immunomodulatory properties and in vivo osteogenesis of human dental stem cells from fresh and cryopreserved dental follicles.

In our previous study, dental follicle tissues from extracted wisdom teeth were successfully cryopreserved for use as a source of stem cells. The goals of the present study were to investigate the immunomodulatory properties of stem cells from fresh and cryopreserved dental follicles (fDFCs and cDFCs, respectively) and to analyze in vivo osteogenesis after transplantation of these DFCs into experimental animals. Third passage fDFCs and cDFCs showed similar expression levels of interferon-γ receptor (CD119) and major histocompatibility complex class I and II (MHC I and MHC II, respectively), with high levels of CD119 and MHC I and nearly no expression of MHC II. Both fresh and cryopreserved human DFCs (hDFCs) were in vivo transplanted along with a demineralized bone matrix scaffold into mandibular defects in miniature pigs and subcutaneous tissues of mice. Radiological and histological evaluations of in vivo osteogenesis in hDFC-transplanted sites revealed significantly enhanced new bone formation activities compared with those in scaffold-only implanted control sites. Interestingly, at 8 weeks post-hDFC transplantation, the newly generated bones were overgrown compared to the original size of the mandibular defects, and strong expression of osteocalcin and vascular endothelial growth factor were detected in the hDFCs-transplanted tissues of both animals. Immunohistochemical analysis of CD3, CD4, and CD8 in the ectopic bone formation sites of mice showed significantly decreased CD4 expression in DFCs-implanted tissues compared with those in control sites. These findings indicate that hDFCs possess immunomodulatory properties that involved inhibition of the adaptive immune response mediated by CD4 and MHC II, which highlights the usefulness of hDFCs in tissue engineering. In particular, long-term preserved dental follicles could serve as an excellent autologous or allogenic stem cell source for bone tissue regeneration as well as a valuable therapeutic agent for immune diseases.

Functional and histological evidence for the targeted therapy using biocompatible polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.

BACKGROUND: Injection of bulking agents into the anal canal is limited by several factors, including biological resorption, particle migration, and ongoing degradation of the injected bulking agent. OBJECTIVE: We investigated whether an injection of polycaprolactone beads containing autologous myoblasts could improve sphincter function in a dog model of fecal incontinence. DESIGN: The control sham surgery group underwent skin incision around the anal sphincter (n = 5). Fecal incontinence was induced by resecting 25% of the posterior internal/external anal sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26-labeled autologous myoblasts. SETTING: This study was conducted at the department of surgery in collaboration with the department of advanced materials. OUTCOME MEASURES: Three months after injection treatment, the resting and contractile pressure differences of the anal sphincter were compared, and histopathological studies were performed. RESULTS: The anal pressures in untreated dogs were significantly lower than those in the sham surgery group (p < 0.05). The resting and contractile pressure differences were higher in treated dogs than in untreated dogs (resting pressure difference: 0.7 ± 0.5 vs -0.6 ± 0.8 mmHg; coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p = 0.001; contractile pressure difference: 1.1 ± 4.2 vs -3.9 ± 2.6 mmHg; coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining confirmed that the myoblasts had differentiated and synthesized myosin heavy chain, as observed in vitro. LIMITATIONS: This study was limited by the lack of comparison of injecting beads containing autologous myoblasts with injecting myoblasts alone. CONCLUSION: This study shows that an injection of polycaprolactone beads containing autologous myoblasts may improve anal sphincter function in an animal model of fecal incontinence.

Coadministration of basic fibroblast growth factor-loaded polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence.

PURPOSE: Basic fibroblastic growth factor (bFGF), a member of the heparin-binding growth factor family, regulates muscle differentiation. We investigated whether coadministration of autologous myoblasts and bFGF-loaded polycaprolactone beads could improve sphincter recovery in a dog model of fecal incontinence (FI). METHODS: FI was induced by resecting 25% of the posterior anal sphincter in ten mongrel dogs. One month later, the dogs were randomized to receive either PKH-26-labeled autologous myoblasts alone (M group, five dogs) or autologous myoblasts and bFGF-loaded polycaprolactone beads (MBG group, five dogs). The outcomes included anal manometry, compound muscle action potentials (CMAPs) of the pudendal nerve, and histology. RESULTS: The increase in anal contractile pressure over 3 months was significantly greater in the MBG group (from 4.85 to 6.83 mmHg) than that in the M group (from 4.94 to 4.25 mmHg), with a coefficient for the difference in recovery rate of 2.672 (95% confidence interval [CI] 0.962 to 4.373, p = 0.002). The change in the CMAP amplitude was also significantly greater in the MBG group (from 0.59 to 1.56 mV) than that in the M group (from 0.81 to 0.67 mV) (coefficient 1.114, 95% CI 0.43 to 1.80, p = 0.001). Labeled cells were detected in 2/5 (40%) and 5/5 (100%) dogs in the M and MBG groups, respectively. CONCLUSION: Coadministration of bFGF-loaded PCL beads and autologous myoblasts improved the recovery of sphincter function in a dog model of FI and had better outcomes than cell-based therapy alone.

Characterization and preparation of bio-tubular scaffolds for fabricating artificial vascular grafts by combining electrospinning and a 3D printing system.

The last decade has seen artificial blood vessels composed of natural polymer nanofibers grafted into human bodies to facilitate the recovery of damaged blood vessels. However, electrospun nanofibers (ENs) of biocompatible materials such as chitosan (CTS) suffer from poor mechanical properties. This study describes the design and fabrication of artificial blood vessels composed of a blend of CTS and PCL ENs and coated with PCL strands using rapid prototyping technology. The resulting tubular vessels exhibited excellent mechanical properties and showed that this process may be useful for vascular reconstruction.

Dual growth factor-loaded in situ gel-forming bulking agent: passive and bioactive effects for the treatment of urinary incontinence.

Stress urinary incontinence (SUI) is one of the major medical problems for adult females and has a devastating effect on their quality of life. The major cause of the development of the SUI is dysfunction of the urethral supporting tissues as a result of aging and childbirth. In this study, in situ gel-forming bulking agent loaded with dual growth factors, nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), was fabricated. The bulking agent consisted of three components; (i) polycaprolactone (PCL) beads, (ii) bFGF-loaded nanogels, and (iii) NGF-loaded in situ gel forming solution. The bulking agent can provide an initial passive bulking effect (from the PCL beads) and regenerate malfunctioning tissues around the urethra (from the sequential and continuous release of growth factors from the hydrogel) for the effective treatment of SUI. The PCL beads were located stably at the applied urethra site (urinary incontinent SD rat) without migration to provide a passive bulking effect. The sequential release of the growth factors (NGF within a week and bFGF for more than 4 weeks) from the bulking agent provided regeneration of damaged nerve and smooth muscle, and thus enhanced biological function around the urethra. From the findings, we suggest that dual growth factor (NGF and bFGF)-loaded in situ gel-forming bulking agent may be a promising injectable bioactive system for the treatment for SUI.

Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model.

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold(heparin-bFGF) group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H2O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H2O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H2O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H2O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft.

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.

Enhancement of the targeting capabilities of the Paclitaxel-loaded pluronic nanoparticles with a glycol chitosan/heparin composite.

An enhancement of tumor-targeting capability was demonstrated with paclitaxel (PTX)-loaded Pluronic nanoparticles (NPs) with immobilized glycol chitosan and heparin. The PTX-loaded Pluronic NPs were prepared as described in our previous report by means of a temperature-induced phase transition in a mixture of Pluronic F-68 and liquid polyethylene glycol (PEG; molecular weight: 400) containing PTX. The liquid PEG is used as the solubilizer of PTX, and Pluronic F-68 is the polymer that encapsulates the PTX. The glycol chitosan and heparin were immobilized on the surface of the Pluronic NPs in an aqueous medium, and a powdery form of the glycol chitosan/heparin immobilized Pluronic NPs (composite NPs) was obtained by freeze-drying. Field emission scanning electron microscopy and a particle size analyzer were used to observe the morphology and size distribution of the prepared NPs. To apply the composite NPs as a delivery system for the model anticancer drug PTX, the release pattern and pharmacokinetic parameters were observed, and the tumor growth was monitored by injecting the composite NPs into the tail veins of tumor-bearing mice. An enhancement of tumor-targeting capability of NPs was verified by using noninvasive live animal imaging technology to observe the time-dependent excretion profile, the in vivo biodistribution, circulation time, and the tumor-targeting capability of composite NPs.

Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury.

INTRODUCTION: Cavernous nerve injury is the main reason for post-prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED. AIM: To evaluate the therapeutic efficacy of adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF) immobilized Poly-Lactic-Co-Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post-prostatectomy ED. Methods. Rats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF-membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF-membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled-released for a period of 4 weeks in a BDNF/PLGA porous membrane system. MAIN OUTCOME MEASURES: Four weeks after the operation, erectile function was assessed by detecting the ratio of intra-cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho-endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively. RESULTS: In the ADSC/BDNF-membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF-membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups. CONCLUSIONS: ADSCs with BDNF-membrane on the cavernous nerve can improve erectile function in a rat model of post-prostatectomy ED, which may be used as a novel therapy for post-prostatectomy ED.

Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue adhesion barrier.

Although hyaluronic acid (HA) has been conventionally utilized as a tissue adhesion barrier material, its rapid clearance in the body still remains as a big challenge in the clinical practice. In this study, we prepared a hydrogel of HA embedded in mildly crosslinked alginate (HA/mcALG hydrogel), which is injectable, easily covers injured tissues, and remains stably at the applied site during wound healing (by muco-adhesive HA embedded in the network structure of the mcALG hydrogel). The HA/mcALG hydrogel was highly effective for the prevention of peritoneal tissue adhesion compared to HA and mcALG hydrogels, and did not lead to any abnormal tissue responses during wound healing. The HA/mcALG hydrogel can be a good candidate as an injectable tissue adhesion barrier for clinical applications.

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration.

Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

Nanoscale film formation of recombinant azurin variants with various cysteine residues on gold substrate for bioelectronic device.

Nanoscale film fabrication of recombinant azurin variants with various cysteine residues on gold substrate was developed without any surface modification for bioelectronic device. We have modified azurin with different number of cysteine residues at its amino acid chain based on site-directed mutagenesis. The resulting recombinant protein, azurin, retained its original redox property in the same manner as native azurin. Recombinant azurin was immobilized on Au substrate by strong affinity between thiol of cysteine and gold. The orientations of recombinant azurin with various cysteine residues immobilized on the Au substrate were analyzed by fluorescence microscope, scanning tunneling microscope, and surface plasmon resonance. Our data revealed that binding activity of recombinant azurin with three cysteine residues on the Au substrate significantly increased in comparison to single residue azurin. Immobilization method of highly oriented recombinant azurin based on cysteine-modification could be useful for the nanoscale film fabrication of nanobiochip.

Core/shell nanoparticles for pH-sensitive delivery of doxorubicin.

Core/shell nanoparticles with lipid core were prepared and characterized as pH-sensitive delivery system of anticancer drug. The lipid core is composed of drug-loaded lecithin and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) tri-block copolymer, F-127). Based on the preparation method in the previous report by us, the freeze-drying of drug-loaded lecithin was performed in the F-127 aqueous solution containing trehalose used as a cryoprotectant to form stabilized core/shell nanoparticles. For the application of core/shell nanoparticles as a pH-sensitive drug delivery system for anticancer drug, doxorubicin was loaded into the core/shell nanoparticles and the drug loading amount and drug release behavior in response to pH change were observed.

Signaling Molecule-Immobilized Porous Particles with a Leaf-Stacked Structure as a Bioactive Filler System.

The ultimate purpose of this study was to develop a bioactive filler system that would allow volume restoration (passive property) and continuous release of signaling molecules to recruit soft tissues (bioactive property) and thus effectively correct facial aging. To achieve this, we prepared porous particles with a leaf-stacked structure throughout the entire particle volume (LSS particles) using a simple heating-cooling technique. LSS particles were loaded with insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) separately, by immersing the particles in signaling molecule-containing solutions for target tissue recruitment (adipose by IGF-1 and blood vessels by VEGF). IGF-1 and VEGF were continuously released from LSS particles for 28 and 21 days in vitro, respectively, even without additional chemical/physical modifications, because of the unique morphology of the particles. Signaling molecules preserved their bioactivity in vitro (induction of adipogenic and angiogenic differentiation) and in vivo (recruitment of fat and blood vessels) for a sufficient period. Moreover, it was observed that the LSS particles themselves have stable volume retention characteristics in the body. Thus, we suggest that the signaling molecule-loaded LSS particles can function as a bioactive filler system for volume retention and target tissue regeneration.

Fabrication of nano scaled protein monolayer consisting of cytochrome c on self-assembled 11-MUA layer for bioelectronic device.

The biomolecular/organic hetero-structure films (cytochrome c/11-mercapto-undecanoic acid) on gold substrates were controlled and fabricated with molecular level for developing valuable molecular electronic devices. Cytochrome c is a metalloprotein having redox property, which can be directly applicable to biomemory device as a active element. For efficient immobilization of the protein on the gold substrate, 11-mercapto-undecanoic acid (11-MUA) was used as a linker material between protein and inorganic substrate. The proposed nano scaled biomolecular/organic hetero-structure layer (cytochrome c/11-MUA) on gold surface was investigated by using surface plasmon resonance technique. The molecular morphology of the fabricated protein layer was confirmed by scanning tunneling microscopy. Electrochemical properties of fabricated biomolecular/organic hetero layer were verified using cyclic voltammetry. Their redox properties was sustained over 1000 cycles of cyclic voltametry. It proved that the fabricated film was a suitable platform for the bioelectronic device application.

The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver Injury.

Background/Aims: For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model. Methods: A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold. Later, the ADSCs were cultured in hepatic differentiation medium for 2 weeks by a 3-step method. For in vivo experiments, Foxa2-overexpressing ADSCs were loaded in the scaffold, cultured in hepatic differentiation medium and later were implanted in the dorsa of nude mice subjected to acute liver injury (thioacetamide intraperitoneal injection). Results: Foxa2-overexpressing ADSCs showed greater increases in hepatocyte-specific gene markers (alpha fetoprotein [AFP], cytokeratin 18 [CK18], and albumin), cytoplasmic glycogen storage, and cytochrome P450 expression than cells that underwent the conventional differentiation method. In vivo experiments using the nude mouse model showed that 2 weeks after scaffold implantation, the mRNA expression of AFP, CK18, dipeptidyl peptidase 4 (CD26), and connexin 32 (CX32) was higher in the Foxa2-overexpressing ADSCs group than in the ADSCs group. The Foxa2-overexpressing ADSCs scaffold treatment group showed attenuated liver injury without stem cell homing in the thioacetamide-induced acute liver injury model. Conclusions: Foxa2-overexpressing ADSCs applied in a scaffold system enhanced hepatocyte-like differentiation and attenuated acute liver damage in an acute liver injury model without homing effects.