Hiroaki Komuro

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (37)51.61 Total impact

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    ABSTRACT: [Background] A gelatin sponge with slowly releasing basic fibroblast growth factor (b-FGF) enhances chondrogenesis. This study investigated the optimal amount of basic fibroblast growth factor (b-FGF) in gelatin sponges to fabricate engineered cartilage. [Material and Methods] b-FGF (0, 10, 100, 500, 1000 and 2000μg/cm3)-impregnated gelatin sponges incorporating β-tri-calcium-phosphate (β-TCP) were produced. Chondrocytes were isolated from the auricular cartilage of C57B6J mice and expanded. The expanded auricular chondrocytes (10x106cells/cm3) were seeded onto the gelatin sponges, which served as scaffolds. The construct assembly was implanted in the subcutaneous space of mice through a syngeneic fashion. Thereafter, constructs were retrieved at 2, 4 or 6 weeks. [Results]Morphology: The size of implanted constructs was larger than the size of the scaffold with 500, 1000 and 2000μg/cm3 b-FGF-impregnated gelatin sponges incorporating β-TCP at 4 weeks and 6 weeks after implantation.  The weight of the constructs increased roughly proportional to the increase in volume of the b-FGF-impregnated scaffold at 2weeks, 4weeks and 6weeks after implantation, except in the 2000μg/cm3 b-FGF-impregnated constructs group. Histological examination: Extracellular matrix in the center of the constructs was observed in gelatin sponges impregnated with more than 100μg/cm3 b-FGF at 4 weeks after implantation. The areas of cells with abundant extracellular matrix were positive for cartilage-specific marker type 2 collagen in the constructs. ○4Protein assay: Glycosaminoglycan and collagen type 2 expression were significantly increased at 4 and 6 weeks upon implantation of gelatin sponges impregnated with more than 100μg/cm3 b-FGF. At 6weeks after implantation, the ratio of type 2 collagen to type 1 collagen in constructs impregnated with 100μg/cm3 or more b-FGF was higher than that in mice auricular cartilage. [Conclusion] Gelatin sponges impregnated with more than 100μg/cm3 b-FGF incorporating β-TCP with chondrocytes (10x106cells/cm3) can fabricate engineered cartilage at 4 weeks after implantation.
    Tissue engineering. Part A. 10/2014;
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    ABSTRACT: Purpose Our objective was to investigate the feasibility of engineering cartilage on the esophagus layer and outside the esophagus. Moreover, we investigated the feasibility of tracheoplasty with cartilage engineered on the esophagus in rabbits. Methods Chondrocytes were isolated from auricular cartilages. 1. Engineered cartilage formation by histological findings on/into the esophageal layer was compared with that of injectable scaffold and preformed scaffold with chondrocytes. 2. Chondrocytes adhered to gelatin + vicryl mesh™ and b-FGF, were implanted on the outer esophageal surface. Four weeks after seeding, we found that cartilage was implanted in the midposterior portion of the cervical trachea (n = 5), and it was retrieved 8 weeks after seeding. Results 1. A gelatin sponge incorporating β-TCP with vicryl mesh™ showed the best performance for fabricating engineered cartilage on the outer side of the esophagus. 2. Two of 5 rabbits died due to obstructed esophagus. Cartilage engineered outside the esophagus by a composite scaffold as the main material in the gelatin sponge, maintained the airway structure for up to 1 month after implantation. Tracheal epithelial regeneration occurred in the internal lumen of this engineered cartilage. Conclusion Tracheoplasty with cartilage engineered outside the esophagus may be useful for reconstructing airways.
    Journal of Pediatric Surgery. 01/2014;
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    ABSTRACT: Although myoblast transplantation is an attractive method for muscle regeneration, its efficiency remains limited. The efficacy of myoblast transplantation in combination with the controlled and sustained delivery of basic fibroblast growth factor (bFGF) was investigated. Defects of thigh muscle in Sprague-Dawley (SD) rats were created, and GFP-positive myoblasts were subsequently transplanted. The rats were divided into three groups. In control group 1 (C1) only myoblasts were transplanted, while in control group 2 (C2) myoblasts were introduced along with empty gelatin hydrogel microspheres. In the experimental group (Ex), myoblasts were transplanted along with bFGF incorporated into gelatin hydrogel microspheres. Four weeks after transplantation, GFP-positive myoblasts were found to be integrated into the recipient muscle and to contribute to muscle fibre regeneration in all groups. A significantly higher expression level of GFP in the Ex group demonstrated that the survival rate of transplanted myoblasts in Ex was remarkably improved compared with that in C1 and C2. Furthermore, myofibre regeneration, characterized by centralization of the nuclei, was markedly accelerated in Ex. The expression level of CD31 in Ex was higher than that in both C1 and C2, but the differences were not statistically significant. A significantly higher expression level of Myogenin and a lower expression level of MyoD1 were both observed in Ex after 4 weeks, suggesting the promotion of differentiation to myotubes. Our findings suggest that the controlled and sustained release of bFGF from gelatin hydrogel microspheres improves the survival rate of transplanted myoblasts and promotes muscle regeneration by facilitating myogenesis rather than angiogenesis. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 04/2013; · 4.43 Impact Factor
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    ABSTRACT: Tracheomalacia is a major cause of morbidity in conditions such as oesophageal atresia. However, symptoms usually improve with age. A more rapid growth of tracheal cartilage can be induced by basic-Fibroblast Growth Factor (b-FGF). This study aimed to investigate whether slow-release b-FGF could act as a novel treatment for tracheomalacia. Biodegradable gelatin hydrogel sheets incorporating 0.5, 5, or 50μg/20μl of b-FGF solution were inserted between the cervical trachea and esophagus of rats. No intervention was performed in rats in a control group. All animals were sacrificed 4weeks later, and the luminal area of the cervical trachea and the thickness of the cartilage were measured. The mean luminal areas in the control group and in the b-FGF groups were 3.1, 3.2, 3.8, and 2.6mm(2), respectively, and showed a peak area at 5μg of b-FGF. A significant difference was seen only between the control group and the b-FGF 5μg group (p<0.05). The mean thickness of the tracheal cartilage was 0.12, 0.13, 0.19, and 0.32mm in the control and the b-FGF groups, respectively, and showed a dose-dependent increase, which was statistically significant between the b-FGF 5μg or 50μg groups and the control group (p<0.01). This study showed that slow-release b-FGF enlarges the tracheal lumen and thickens the cartilage in a dose-dependent fashion.
    Journal of Pediatric Surgery 02/2013; 48(2):288-92. · 1.38 Impact Factor
  • Hiroaki Komuro, Noriko Hoshino
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    ABSTRACT: The authors report on 3 infants below 6 months of age at diagnosis, with cervicomediastinal neuroblastoma who presented with life-threatening tracheal obstruction as an oncologic emergency. These neuroblastomas were characterized by favorable biology and chemoresistance. All initially grew rapidly before spontaneously regressing. Nerve injuries occurred in all patients as a result of tumor location. Maintenance of the airway until the expected spontaneous regression was a critical component in the management of these patients.
    Journal of Pediatric Hematology/Oncology 12/2012; · 0.97 Impact Factor
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    ABSTRACT: We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment.
    Journal of Pediatric Surgery 12/2012; 47(12):e21-e25. · 1.38 Impact Factor
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    ABSTRACT: Neuroblastoma (NB) is a highly metastatic tumor in children. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. This study investigated the role of EMT in the progression of NB. Using EMT assays on samples from 11 tumors, we identified 14 genes that were either differentially expressed between tumors of different stages or highly upregulated in NB. Quantitative RT‑PCR of these genes was conducted in 96 NB tumors and their expression levels were compared between stages and between tumors with the presence and absence of MYCN amplification. The association of survival rate with differential gene expression was investigated. Expression of KRT19 was significantly decreased in stage 3 or 4 NB as well as stage 4S NB compared with stage 1 or 2 NB. Expression levels of KRT19 and ERBB3 were significantly low, and expression levels of TWST1 and TCF3 were high in MYCN‑amplified NB. The patients with low expression of KRT19 or ERBB3 showed significantly worse overall survival. Furthermore, the correlation between high invasive ability and low expression of KRT19 and ERBB3 was suggested in vitro using six NB cell lines. The authors conclude that downregulation of KRT19 is highly associated with tumor progression in NB and metastasis in localized primary NB and that low expression of ERBB3 is also associated with progression of NB.
    International Journal of Oncology 11/2012; · 2.66 Impact Factor
  • Hiroaki Komuro, Chikashi Gotoh
    Pediatric Radiology 08/2012; 42(10):1267-8. · 1.57 Impact Factor
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    ABSTRACT: Pancreatitis, a late complication of an annular pancreas (AP), results from coexisting pancreaticobiliary malformations including pancreas divisum (PD), and pancreaticobiliary maljunction (PBM). The authors report the case of a 3-year-old boy with an unusual type of AP in which the dorsal anlage encircled the duodenum. The patient developed duodenal obstruction as well as duodenopancreatic reflux with resulting hyperamylasemia and hyperlipasemia. This type of AP associated with duodenopancreatic reflux in AP has not been reported previously. The patient was successfully treated by duodenoduodenostomy, which, by correcting the duodenopancreatic reflux, prevented the later development of pancreatitis.
    Pediatric Surgery International 02/2012; 28(7):715-7. · 1.22 Impact Factor
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    ABSTRACT: The aim of the study was to identify the clinical characteristics and outcome of patients with liver fibrosis in choledochal cyst (CC). Forty patients with CC who underwent liver biopsy were included. Liver fibrosis was classified as follows: grade 0, no fibrosis; grade 1, mild fibrosis localized in the portal area; grade 2, moderate fibrosis with occasional bridging; and grade 3, severe fibrosis with diffuse bridging. Fourteen patients (35%) had liver fibrosis. Patients in the fibrosis group were significantly younger (1.2 vs 2.7 years) and had higher total bilirubin (5.3 vs 2.6 mg/dL). Severity of liver fibrosis was inversely correlated with age (P = .044). Amylase and lipase in bile were significantly lower in the fibrosis group (amylase, 531 vs 15,000 U/L; lipase, 783 vs 23,100 U/L). Postoperative serum analysis demonstrated no differences between the two groups. Most patients in both groups had normal aspartate aminotransferase, alanine aminotransferase, total bilirubin, and γ-glutamyl transpeptidase regardless of severity of fibrosis. Postoperative biliary complication or cholangiocarcinoma was not found in the fibrosis group. Our data suggest that liver fibrosis is mainly influenced by obstructive cholangiopathy rather than refluxed pancreatic secretion. Prognosis of patients with CC and liver fibrosis was as good as that of patients without fibrosis.
    Journal of Pediatric Surgery 12/2011; 46(12):2296-300. · 1.38 Impact Factor
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    ABSTRACT: The aim of this study is to investigate the clinical characteristics of cases of duodenal atresia (DA) which present with bowel gas distal to a typical double-bubble sign through an anomalous bile duct conduit. Medical records of 57 neonates with duodenal obstruction (atresia or stenosis), presenting with a double-bubble sign and treated at our institute from 1978 to 2010, were retrospectively reviewed. Thirteen (23%) of 57 neonates presented with bowel gas distal to the double-bubble sign. Passage of gas through the duodenal stenosis may have occurred in 3 cases, whereas in 9 cases, gas may have bypassed the atresia through an anomalous bifurcated bile duct termination and through the pancreatic duct from the accessory to the main pancreatic duct in one case. A preoperative upper gastrointestinal series was performed in 9 cases, and an anomalous bifurcated bile duct conduit was demonstrated in 5 cases. Severe and prolonged cholestasis necessitating evaluation for biliary atresia was found in 2 patients with anomalous bile duct anatomy. Neonatal DA presenting with distal bowel gas via an anomalous bifurcated bile duct conduit is more common than initially thought and occurs more frequently than duodenal stenosis. These patients might be at risk for cholestasis, possibly owing to duodeno-biliary reflux through the ampulla.
    Journal of Pediatric Surgery 12/2011; 46(12):2301-4. · 1.38 Impact Factor
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    ABSTRACT: Enteric duplication cyst is one of the rarest forms of cystic lesion of the pancreas. We report a unique case of an enteric duplication cyst of the pancreas that was communicating with a duplicated pancreatic duct. A 7-year-old girl with severe acute abdominal pain was found to have a large cyst that was smoothly communicating with the dilated pancreatic duct in the pancreatic tail. Analysis of cyst fluid showed elevated levels of amylase, carcinoembryonic antigen (CEA) and CA 19-9, and no epithelial cells. Intraoperative cyst pancreatography revealed that the pancreatic duct was duplicated in the tail: 1 duct was communicating with the cyst, and the other was dilated within the pancreatic tail. The patient underwent spleen-preserving distal pancreatectomy and complete cyst excision without complication. Because preoperative diagnosis of duplication cyst of the pancreas is difficult, this condition should be considered during differential diagnosis of atypical cystic lesions of the pancreas. Complete excision is desirable for the management of duplication cyst of the pancreas.
    Journal of Pediatric Surgery 08/2011; 46(8):e13-6. · 1.38 Impact Factor
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    ABSTRACT: The pathogenesis of gastroschisis is unknown. It may be helpful in understanding its pathogenesis to know the structural relationships among umbilical components including umbilical vessels, urachus, and vitelline structures, and thus, the authors investigated the remnants of vitelline structures in a series of cases of gastroschisis. Medical records of 41 cases with gastroschisis treated in our institute from 1979 to 2009 were retrospectively reviewed. Paraumbilical bands, possible remnants of vitelline structures, were observed in 4 cases (9.8%). All 4 bands were attached to the skin edge of the abdominal defect without incorporation into the umbilical cord. The band ended at the mesentery in 3 cases and at the antimesenteric site of the ileum in the remaining case. Histologic findings showed fibrous tissues in all cases. One was possibly associated with the development of colonic atresia. Another was noticed after silo reduction when herniated bowels became strangulated by the band. The other 2 cases were uncomplicated. Our findings may support the recently proposed hypothesis that the developmental failure of the yolk sac and related vitelline structures to merge with or to be incorporated into the umbilical stalk might be associated with the pathogenesis of the abdominal wall defect in gastroschisis. Paraumbilical bands derived from vitelline structures may possibly cause intestinal ischemia prenatally or postnatally.
    Journal of Pediatric Surgery 10/2010; 45(10):2025-9. · 1.38 Impact Factor
  • Journal of Pediatric Surgery 08/2010; 45(8):1748-50. · 1.38 Impact Factor
  • Yukihiro Tatekawa, Hiroaki Komuro
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    ABSTRACT: Gastroparesis is a symptomatic chronic disorder of the stomach characterized by delayed gastric emptying in the absence of mechanical obstruction. Gastroparesis has been associated with various diseases and may occur as part of a mitochondrial disorder. In a patient with pyruvate dehydrogenase complex deficiency, which is associated with abnormal mitochondrial metabolism, intragastric liquids were retained massively and gastroparesis was diagnosed by demonstrating delayed gastric emptying. For an atonic stomach with impaired fundic distention, partial gastric plication, modified stomach-partitioning gastrojejunostomy using the stapled gastrectomy with Braun's anastomosis, antireflux gastroplasty with stapled wedge, and re-gastrostomy were performed. After operation, intragastric liquids were reduced remarkably and delayed gastric emptying was improved. She was doing well and discharged uneventfully. Our technical surgery reported improvement in delayed gastric emptying and we confirm the benefits of this operation.
    Pediatric Surgery International 06/2010; 26(6):655-8. · 1.22 Impact Factor
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    ABSTRACT: We studied the regenerated cartilage in tracheal defect repair and compared the bio-materials used versus native trachea using basic fibroblast growth factor (bFGF)-impregnated gelatin hydrogel. A full-thickness anterior defect was created in the cervical trachea of 15 experimental rabbits. The defect was implanted with a hybrid scaffold of poly(lactic-co-glycolic acid) (PLGA) knitted mesh and collagen sponge. The implanted trachea was reinforced with a copolymer stent of polycaprolactone and poly(lactic acid) coarse fiber mesh. A gelatin hydrogel was used for providing a sustained release of bFGF. The reconstructed tracheas were divided into three groups with wrapped materials; without gelatin hydrogel (control group, n = 5), a gelatin hydrogel with saline (gelatin group, n = 5), and a gelatin hydrogel with 100 microg of bFGF (bFGF group, n = 5). One of the five rabbits in each group at 1 month after operation, one at 3 months, and three at 6 months were killed and the engineered tracheas were evaluated histologically. Biomechanical properties were evaluated on samples at 6 months postoperatively. The rigid support in the defect portion was maintained during 6 months postoperatively. The newly regenerated cartilages were recognized between the host cartilage stumps at 3 months postoperatively in the bFGF group, and limited new cartilage growth and epithelialization were observed at 6 months postoperatively. The experiment shows that using bFGF, better mechanical strength was obtained but with poor cartilage growth.
    Pediatric Surgery International 06/2010; 26(6):575-80. · 1.22 Impact Factor
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    ABSTRACT: Amniotic epithelial cells (AEC) are thought to represent a stem-like cell population and to be an attractive cell source for regenerative medicine, because abundant cells can be obtained noninvasively at delivery. The authors investigated the neural differentiation potential of rat AEC. Rat AEC expressed vimentin and nestin, but not c-kit, oct-4, or nanog. The expression of the neural lineage markers, including betaIII-tubulin, neuron specific enolase (NSE), neurofilament-M, neuroD, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), tyrosine hydroxylase (TH), acetylcholinesterase (AChE), cholin acetyltransferase (ChAT), and mammalian achaete-scute homolog1 (MASH1), was detected by RT-PCR in the cultured rat AEC. After neural induction, rat AEC dramatically changed their shapes, projecting dendrite-like structures. Immunocytochemically, approximately 20% of the induced cells expressed an immature neuronal marker, betaIII-tubulin. Our findings suggested that rat AEC might be already committed to differentiate to various neural lineages and that they could differentiate to immature neurons in vitro.
    Fetal and pediatric pathology 01/2010; 29(3):133-43. · 0.36 Impact Factor
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    ABSTRACT: Infants with higher anorectal anomalies often develop fecal incontinence after surgical reconstruction mainly due to the incomplete development of defecation muscles. We investigated the possibility of defecation muscle regeneration by myoblast transplantation to improve fecal continence. Myoblasts from F344 female rats at ages of 1 day, 1, 2, 3, 4, 8, and 12 weeks were prepared by a preplating method. In vivo muscle differentiation of myoblasts was evaluated using immunofluorescence after transplantation of GFP-positive myoblasts into nude mice, the damaged thigh muscles, and the levator ani muscle of GFP-negative rats. The ratios of myoblasts obtained from 1 day, 1, 2, 3, 4, 8, and 12-week-old rats were 35, 71, 65, 61, 52, 44, and 23%, respectively. Myotube formation by transplanted myoblasts was observed in the back of nude mice. Myoblasts transplanted into damaged thigh muscles were integrated into recipient muscles with myofiber formation. Transferred myoblasts formed myotubes surrounding the levator ani muscle, although myofiber formation was not observed. Myoblasts were most efficiently obtained from juvenile rats. Myoblast transplantation may provide a novel treatment strategy for improving fecal continence after repair of anorectal anomalies in infants.
    Pediatric Surgery International 09/2009; 25(11):981-6. · 1.22 Impact Factor
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    ABSTRACT: We investigated epithelialization and newly formed cartilage in an artificial trachea constructed using a bioabsorbable copolymer. Fifteen male Japanese white rabbits (2.5-2.8 kg) were divided into three groups. A full-thickness anterior defect (4 mm x 10 mm) was created in the trachea. The defect was implanted with one of the following bioabsorbable copolymers: caprolactone-lactide copolymer sponge sheet reinforced with poly(glycolic acid) fiber mesh (Cop) (n = 6, group A), Cop-incorporating gelatin hydrogel (n = 4, group B), and Cop-incorporating gelatin hydrogel with 100 microg of basic fibroblast growth factor (n = 5, group C). Each trachea was reinforced with an external nondegradable polymer stent. Three rabbits in each group were sacrificed at 1, 3, and 6 mo postoperatively and the trachea was evaluated histologically; other animals were sacrificed up to 12 mo postoperatively. In groups A, B, and C there were two, one, and one postoperative deaths, respectively. In group A, epithelialization was recognized from 1 mo to 12 mo postoperatively, but no new cartilage was formed during the 12 mo following implantation. In group B, epithelialization was recognized 3 and 6 mo postoperatively, and new cartilage was detected at 6 mo after the operation. In group C, newly formed cartilage and epithelialization were observed 3, 6, and even 12 mo postoperatively. Furthermore, neovascularization was observed in groups B and C. A bioabsorbable copolymer incorporating gelatin hydrogel induces tracheal epithelialization and formation of cartilage and vessels in tracheal defects, and could be available for clinical use in children.
    Journal of Surgical Research 01/2009; 160(1):114-21. · 2.02 Impact Factor
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    ABSTRACT: Patch closure is necessary to achieve tension-free repair in large congenital diaphragmatic hernia. However, the use of prosthetic material may lead to granulation, allergic reaction, infection, recurrence of hernia, and thoracic deformity. Tissue engineering may become an alternative treatment strategy for diaphragmatic hernia repair, since the regenerated autologous tissue is expected to grow potentially without rejection or infection. We evaluated the efficacy of diaphragmatic hernia repair in a rat model using a poly-lactic-co-glycolic acid (PLGA) mesh-collagen sponge hybrid scaffold, designed for in situ tissue engineering. Twenty-four F344 female rats were used. Oval-shaped defects were surgically created in the left diaphragm and repaired with three different grafts, including PLGA mesh in group 1 (n = 7), PLGA mesh-collagen sponge hybrid scaffold in group 2 (n = 7), and PLGA mesh-collagen sponge hybrid scaffold seeded with bone marrow-derived mesenchymal stem cells (MSCs) in group 3 (n = 10). The animals were killed at 1, 2, and 3 months after operation. The specimens were examined macroscopically and microscopically. No recurrence or eventration was observed. In all animals, autologous fibrous tissue with vascularization was generated at the graft site. Although no muscular tissue was detected, scattered desmin-positive cells were observed in groups 2 and 3. The 'neodiaphragm' in groups 2 and 3 was significantly thicker compared with that in group 1. There was no significant difference in the 'neodiaphragm' between groups 2 and 3. The PLGA mesh-collagen sponge hybrid scaffold provided better promotion of autologous in situ tissue regeneration in the diaphragm, suggesting its potential application to diaphragmatic repair in place of other prosthetic patches.
    Pediatric Surgery International 10/2008; 24(9):1041-5. · 1.22 Impact Factor