Embolization of hepatic arterioportal shunt with ethanol-soaked gelatin sponge.

OBJECTIVE: The objective of this study is to investigate the effect of ethanol-soaked gelatin sponge (ESG) in the treatment of hepatic arterioportal shunt (APS). METHODS: Hepatocellular carcinoma (HCC) patients with APS were divided into experimental group (Group E) and control group (Group C). Patients in Group E were treated with ESG for APS embolization, whereas patients in Group C were treated with polyvinyl alcohol particles for APS embolization, with other treatment unchanged. APS and the Eastern Cooperative Oncology Group (ECOG) physical status scores of patients before and after the first treatment and further consultation in the 6th week and the survival rate in follow-up visit were recorded. The changes of liver function during treatment were monitored. RESULTS: Before the first treatment, there was no statistical significant difference in APS between two groups. After that, APS in Groups E (P = 2.49 × 10-7) and C (P = 2.10 × 10-4) was improved. In further consultation, APS in Groups E (P = 2.73 × 10-13) and C (P = 2.90 × 10-8) was further improved after examinations and corresponding treatment. After the first treatment and further consultation, APS score was lower in Group E than in Group C, and there were still five patients whose APS score was 2 in Group C. Quality of life in two groups was effectively controlled without getting worse and the ECOG score reduced. Liver function in the two groups did not worsen with the use of liver protective drugs. No deaths occurred in Group E, whereas two patients died in Group C during treatment and follow-up visit. CONCLUSION: The results show that ESG can effectively reduce APS score and improve the survival rate of HCC patients.

Comparison between different isoelectric points of biodegradable gelatin sponges incorporating ß-tricalcium phosphate and recombinant human fibroblast growth factor-2 for ridge augmentation: A preclinical study of saddle-type defects in dogs.

BACKGROUND AND OBJECTIVE: It is well known that recombinant human fibroblast growth factor-2 (rhFGF-2) signaling plays an important role in tissue repair and regeneration. rhFGF-2 strongly binds to acidic gelatin via ionic linkages and is gradually released upon gelatin decomposition. On the other hand, the linkage between rhFGF-2 and basic gelatin is so weak that most rhFGF-2 is rapidly released from basic gelatin by simple desorption. Gelatin/ß-tricalcium phosphate (ß-TCP) sponges, which comprise 50 wt% gelatin and 50 wt% ß-TCP in a cross-linked structure, can release rhFGF-2 gradually owing to their electrical features. In a previous study, we reported that new bone height in the test group using rhFGF-2 with acidic gelatin/ß-TCP sponges was significantly greater than that in the control group using acidic gelatin/ß-TCP sponges alone in a ridge augmentation model in dogs. However, whether these results depend on controlled release by the gelatin/ß-TCP sponges remains controversial. In this study, we evaluated the effects of controlled release by comparing acidic and basic gelatin/ß-TCP sponges with different isoelectric points (IEP) on ridge augmentation in dogs. MATERIALS AND METHODS: Twelve weeks after extraction of the maxillary second and third incisors of six dogs, critically sized saddle-type defects (8 mm length × 4 mm depth) were surgically created bilaterally 2 mm from the mesial side of the canine. Acidic gelatin/ß-TCP sponges (IEP 5.0) soaked with 0.3% rhFGF-2 were applied to the defect in the acidic group, whereas basic gelatin/ß-TCP sponges (IEP 9.0) soaked with 0.3% rhFGF-2 were applied to the defect in the basic group. Twelve weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography (micro-CT) and histological analyses. RESULTS: New bone area detected by micro-CT analysis was significantly smaller in the basic group than in the acidic group. New bone height calculated by histologic sections was significantly lower in the basic group than in the acidic group. The total tissue height was lower in the basic group than in the acidic group. However, the differences between both sites were not significant. CONCLUSIONS: These findings suggest that in ridge augmentation of saddle-type defects, controlled release of rhFGF-2 induces notably more alveolar bone formation than does short-term application of rhFGF-2.

Comparative study of electrical and rheological properties of different solutions used in endoscopic mucosal resection.

BACKGROUND AND AIM: The study of electrical and rheological properties of solutions to carry out endoscopic resection procedures could determinate the best candidate. An ex vivo study with porcine stomachs was conducted to analyze electrical resistivity (R) and rheological properties (temperature, viscosity, height and lasting of the cushion) of different substances used in these techniques. METHODS: Tested solutions were: 0.9% saline (S), platelet-rich plasma (PRP), Gliceol (GC), hyaluronic acid 2% (HA), Pluronic-F127 20% (PL), saline with 10% glucose (GS), Gelaspan (GP), Covergel-BiBio (TB) and PRP with TB (PRP+TB). Measurements of electrical and rheological properties were done at 0, 15, 30, 45 and 60 min after submucosal injection. RESULTS: Solutions showed a wide variability of transepithelial R after submucosal injection. Substances able to maintain the highest R 60 min postinjection were TB (7 × 104 Ω), HA (7 × 104 Ω) and PL (7 × 104 Ω). Protective solutions against deep thermal injury (Tª lower than 60°C) were PL (47.6°C), TB (55°C) and HA (56.63°C). Shortest time to carry out resections were observed with GC (17.66″), PRP (20.3″) and GS (23.45″). Solutions with less cushion decrease (<25%) after 60 min were TB (11.74%), PL (18.63%) and PRP (22.12%). CONCLUSIONS: Covergel-BiBio, PL and HA were the best solutions with long-term protective effects (transepithelial R, lower thermal injury and less cushion decrease). Solutions with quicker resection time were GC, PRP and GS.

A retrospective analysis of the efficacy of microparticle-mediated chemoembolization in liver metastases arising from gastrointestinal tumors.

PURPOSE: We evaluated the clinical efficacy of gelatin sponge microparticle (GSM) -mediated chemoembolization for the treatment of patients with liver metastases following surgery for gastrointestinal tumors. MATERIALS AND METHODS: In a retrospective analysis of 37 patients who were treated at our hospital with GSM-mediated chemoembolization for liver metastases over 13 years, we evaluated outcomes using a modified response evaluation criteria in solid tumors system and also assessed liver function and adverse effects. All patients had previously undergone surgery for gastrointestinal tumors. RESULTS: Treatment produced various degrees of necrosis and shrinkage of lesions among our patients. Two patients achieved a complete response (CR), 27 showed a partial response (PR), five had stable disease, and three had progressive disease. The overall response rate (CR + PR) was 78%, and no severe adverse effects were observed. CONCLUSION: GSM-mediated chemoembolization showed good clinical efficacy in the treatment of liver metastases after gastrointestinal tumor surgery. However, larger cohort and clinical controlled studies are warranted.

Chitosan Dextran gel as an anti adhesion agent in a postlaminectomy spinal sheep model.

INTRODUCTION: Post-operative peridural adhesions increase morbidity after neurosurgical procedures. Aim of this study is to assess safety and efficacy of Chitosan-Dextran (CD) gel as an anti-adhesion agent in a spinal laminectomy sheep model. METHODS: Eighteen sheep were used in this study with 6 animals in each treatment arm (namely, CD gel, Gelfoam paste and normal saline control). Posterior lumbar laminectomy was performed in all animals and the dura was exposed intact. Test agents were applied over the exposed dura and the wound was closed in layers. Sheep were euthanized at the end of three months. MRI spine was performed after euthanasia to assess epidural fibrosis. Adhesion in the spinal specimen was assessed by Peel test and histopathology was used to assess safety of the agents. RESULTS: Average scores for the Peel test for CD gel, Gelfoam and normal saline control groups were 1.16 (95% CI, 0.5-1.7), 1.5 (95% CI, 0.6-2.3) and 3 (95% CI, 2.1-3.8) respectively. There was significant reduction in adhesions between treatment and normal saline treated groups (p=0.0292), with no difference between Gelfoam and CD gel groups (p=0.56). Average scores on MRI for CD gel, Gelfoam and normal saline groups were 1.4 (95% CI, 0.9-1.8), 1.5 (95% CI, 1.2-1.8) and 1.6 (95% CI, 1.3-1.8) respectively, with no significant difference in fibrosis amongst (p=0.2992). Histopathology did not show any adverse effects. CONCLUSION: CD gel is an effective agent to reduce epidural adhesions with a good safety profile in neural tissue.

Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of Gastric Variceal Hemorrhage.

OBJECTIVE: To evaluate the feasibility, safety, and clinical outcomes of plug-assisted retrograde transvenous obliteration (PARTO) to treat gastric variceal hemorrhage in patients with portal hypertension. MATERIALS AND METHODS: From May 2012 to June 2014, 19 patients (11 men and 8 women, median age; 61, with history of gastric variceal hemorrhage; 17, active bleeding; 2) who underwent PARTO using a vascular plug and a gelfoam pledget were retrospectively analyzed. Clinical and laboratory data were examined to evaluate primary (technical and clinical success, complications) and secondary (worsening of esophageal varix [EV], change in liver function) end points. Median follow-up duration was 11 months, from 6.5 to 18 months. The Wilcoxon signed-rank test was used to compare laboratory data before and after the procedure. RESULTS: Technical success (complete occlusion of the efferent shunt and complete filling of gastric varix [GV] with a gelfoam slurry) was achieved in 18 of 19 (94.7%) patients. The embolic materials could not reach the GV in 1 patient who had endoscopic glue injection before our procedure. The clinical success rate (no recurrence of gastric variceal bleeding) was the same because the technically failed patient showed recurrent bleeding later. Acute complications included fever (n = 2), fever and hypotension (n = 2; one diagnosed adrenal insufficiency), and transient microscopic hematuria (n = 3). Ten patients underwent follow-up endoscopy; all exhibited GV improvement, except 2 without endoscopic change. Five patients exhibited aggravated EV, and 2 of them had a bleeding event. Laboratory findings were significantly improved after PARTO. CONCLUSION: PARTO is technically feasible, safe, and effective for gastric variceal hemorrhage in patients with portal hypertension.

Polymeric materials for embolic and chemoembolic applications.

Percutaneous transcatheter embolization procedures involve the selective occlusion of blood vessels. Occlusive agents, referred to as embolics, vary in material characteristics including chemical composition, mechanical properties, and the ability to concurrently deliver drugs. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives, in situ gelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackable in vivo. This article reviews commercially available materials used for embolization as well as polymeric materials that are under investigation.

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

Traditional Chinese medicine herbal mixture LQ arrests FUCCI-expressing HeLa cells in G0/G1 phase in 2D plastic, 2.5D Matrigel, and 3D Gelfoam culture visualized with FUCCI imaging.

We used the fluorescence ubiquitination-based cell cycle indicator (FUCCI) to monitor cell cycle arrest after treatment of FUCCI-expressing HeLa cells (FUCCI-HeLa) with a traditional Chinese medicine (TCM) herbal mixture LQ, previously shown to have anti-tumor and anti-metastatic activity in mouse models. Paclitaxel was used as the positive control. In 2D monolayer culture, the untreated control had approximately 45% of the cells in S/G2/M phase. In contrast, the LQ-treated cells (9 mg/ml) were mostly in the G0/G1 (>90%) after 72 hours. After treatment with paclitaxel (0.01 µm), for 72 hours, 95% of the cells were in S/G2/M. In 2.5D Matrigel culture, the colonies in the untreated control group had 40% of the cells in S/G2/M. LQ arrested the cells in G0/G1 after 72 hours. Paclitaxel arrested almost all the cells in S/G2/M after 72 hours. In 3D Gelfoam culture, the untreated control culture had approximately 45% of cells in G2/M. In contrast, the LQ-treated cells were mostly in G0/G1 phase (>80%) after 72 hours treatment. Paclitaxel resulted in 90% of the cells arrested in S/G2/M after 72 hours. The present report suggests the non-toxic LQ has potential to maintain cancers in a quiescent state for long periods of time.

3-dimensional tissue is formed from cancer cells in vitro on Gelfoam®, but not on Matrigel™.

Cell and tissue culture can be performed on different substrates such as on plastic, in Matrigel™, and on Gelfoam(®), a sponge matrix. Each of these substrates consists of a very different surface, ranging from hard and inflexible, a gel, and a sponge-matrix, respectively. Folkman and Moscona found that cell shape was tightly coupled to DNA synthesis and cell growth. Therefore, the flexibility of a substrate is important for cells to maintain their optimal shape. Human osteosarcoma cells, stably expressing a fusion protein of α(v) integrin and green fluorescent protein (GFP), grew as a simple monolayer without any structure formation on the surface of a plastic dish. When the osteosarcoma cells were cultured within Matrigel™, the cancer cells formed colonies but no other structures. When the cancer cells were seeded on Gelfoam(®), the cells formed three-dimensional tissue-like structures. The behavior of 143B osteosarcoma cells on Gelfoam(®) in culture is remarkably different from those of these cells in monolayer culture or in Matrigel™. Tissue-like structures were observed only in Gelfoam(®) culture. The data in this report suggest a flexible structural substrate such as Gelfoam(®) provides a more in vivo-like culture condition than monolayer culture or Matrigel(TM) and that Matrigel(TM) does not result in actual three-dimensional culture.

Graft of a tissue-engineered neural scaffold serves as a promising strategy to restore myelination after rat spinal cord transection.

Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI.

Assessment of the regenerative potential of allogeneic periodontal ligament stem cells in a rodent periodontal defect model.

BACKGROUND AND OBJECTIVE: The complex microenvironment of the periodontal wound creates many challenges associated with multitissue regeneration of periodontal lesions. Recent characterization of mesenchymal stem cell-like populations residing in periodontal ligament tissues has shown that these cells exhibit features of postnatal stem cells. Despite these advances, a lack of consistency in design of preclinical studies and a limited study of allogeneic transplantation applications has restricted our understanding of their clinical utility in the treatment of periodontal disease. The aim of this study was to assess the regenerative potential of allogeneic periodontal ligament stem cells (PDLSCs) in a rat periodontal fenestration defect mode and to identify an optimal end time-point suitable for quantitative assessment of tissue regeneration. MATERIAL AND METHODS: Periodontal fenestration defects, created in Sprague Dawley rats, were treated with allogeneic PDLSCs seeded onto Gelfoam(®) (Absorbable gelatin sponge; Pharmacia Corporation, Kalamazoo, MI, USA) or with Gelfoam(®) alone, or remained untreated. Experimental rats were killed at 7, 14, 21 or 28 d after surgery and the tissues were processed for immunohistochemical and histomorphometric examination. RESULTS: Defects treated with PDLSCs showed significantly greater percentage bone fill and length of new bone bridge compared with the untreated group or the group treated with Gelfoam(®) alone on days 14 and 21. Similarly, a statistically significant difference was achieved within specimens retrieved on day 21 for analysis of regeneration of cementum/periodontal ligament (PDL)-like structures. CONCLUSION: The present investigation shows that allogeneic PDLSCs have a marked ability to repair periodontal defects by forming bone, PDL and cementum-like tissue in vivo. The results suggest that treatment periods of 14 and 21 d are optimal end time-points for quantitative assessment of periodontal regeneration within the rodent fenestration-defect model utilized in the present study.

The effect of a gelatin ß-tricalcium phosphate sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2, and platelet-rich plasma (PRP) on equine articular cartilage defect.

We evaluated the curative efficacy of a gelatin ß-tricalcium phosphate (ß-TCP) sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2 (BMP-2), and platelet-rich plasma (PRP) by insertion into an experimentally induced osteochondral defect. A hole of 10 mm diameter and depth was drilled in the bilateral medial femoral condyles of 7 thoroughbred horses, and into each either a loaded sponge (treatment) or a saline-infused ß-TCP sponge (control) was inserted. After 16 weeks, defects were examined by computed tomography, macroscopic analyses, and histological analyses. The median subchondral bone density and macroscopic subscores for joint healing were significantly higher in the treatment legs (P < 0.05). Although there was no significant difference in total histological scores between groups, hyaline cartilaginous tissue was observed across a wider area in the treatment group. Equine joint healing can be enhanced by inserting a BMP-2-, MSC-, and PRP-impregnated ß-TCP sponge at the lesion site.

L'effet d'une éponge de phosphate ß-tricalcique de gélatine imbibée de cellules souches mésenchymateuses (CSM), d'une protéine-2 morphogénétique osseuse et d'un plasma riche en plaquettes (PRP) sur un défaut de cartilage articulaire équin. Nous avons évalué l'efficacité curative d'une éponge de phosphate ß-tricalcique de gélatine (ß-TCP) imbibée de cellules souches mésenchymateuses (CSM), d'une protéine-2 morphogénétique osseuse (P2MO) et d'un plasma riche en plaquettes (PRP) en l'insérant dans un défaut ostéo-cartilagineux induit par expérimentation. Un trou de 10 mm de diamètre et de profondeur a été percé dans les condyles fémoraux médiaux bilatéraux de 7 pur-sang et, chez chaque cheval, une éponge imbibée (traitement) ou une éponge ß-TCP infusée d'une solution saline (témoin) a été insérée. Après 16 semaines, les défauts ont été examinés par tomographie par ordinateur, analyses macroscopiques et analyses histologiques. La densité osseuse sous-chondrale et les sous-notes médianes de la guérison des articulations étaient significativement supérieures dans les jambes traitées (P < 0,05). Même s'il n'y avait pas de différences significatives au niveau des notes histologiques totales entre les groupes, le tissu cartilagineux hyalin a été observé sur une région plus vaste dans le groupe de traitement. La guérison des articulations équines peut être améliorée en insérant une éponge ß-TCP imbibée de P2MO, de CSM et de PRP sur le site de la lésion.(Traduit par Isabelle Vallières).

Clinical evaluation of transcatheter arterial chemoembolization with 2-day-soluble gelatin sponge particles for hepatocellular carcinoma-comparison with insoluble gelatin sponge particles.

PURPOSE: To compare therapeutic effect, adverse events, and embolized hepatic artery impairment in transcatheter arterial chemoembolization between Lipiodol plus insoluble gelatin sponge particles (Gelpart) and Lipiodol plus 2-day-soluble gelatin sponge particles (2DS-GSPs). MATERIALS AND METHODS: In a single-center, prospective, randomized controlled trial, patients with hepatocellular carcinoma were assigned to the 2DS-GSP group or the Gelpart group. Radiographic response at 3 months per modified Response Evaluation Criteria In Solid Tumors was evaluated as the primary endpoint; secondary endpoints were safety (per Common Terminology Criteria for Adverse Events, version 4.0) within 3 months and hepatic branch artery impairment at the time of repeat chemoembolization (grade 0, no damage; grade I, mild vessel wall irregularity; grade II, overt stenosis; grade III, occlusion of more peripheral branch artery than subsegmental artery; grade IV, occlusion of subsegmental artery). Grade II, III, or IV indicated significant hepatic artery impairment. RESULTS: Thirty-seven patients with 143 nodules were randomized to the 2DS-GSP group and 36 patients with 137 nodules were randomized to the Gelpart group. No significant differences in patient background existed between groups. Target lesion response and overall tumor response in the 2DS-GSP and Gelpart groups were 77.7% versus 76.9% and 78.3% versus 77.8%, respectively, with no significant differences. No significant difference in adverse events existed between groups. Hepatic artery impairment was observed in 5% of patients in the 2DS-GSP group (n = 32) and in 16% in the Gelpart group (n = 33; P< .001). CONCLUSIONS: Transcatheter arterial chemoembolization with 2DS-GSPs resulted in the same therapeutic and adverse effects as chemoembolization with Gelpart while causing significantly less hepatic artery impairment.

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors.

BACKGROUND: Surgical tumor resection is the main treatment for tumors however the treatment process often results in massive bleeding and tumor cell residue. The main aim of this research was to address problems such as bleeding, systemic chemotherapy side effects while enhancing quality of life, and increasing drug concentrations at the tumor site by developing a novel formulation with local long-term efficacy for treatment of tumors and to stop bleeding. METHODS: 5-Fluorouracil (5-FU) was suspended in an ethyl acetate solution of poly D,L-lactide-co-glycolic acid (PLGA) and a vacuum drying method was applied. The hemostatic gelatin sponge loaded with 5-FU was prepared by absorption of the suspension. The in vitro and in vivo characteristics of the hemostatic gelatin sponge loaded with 5-FU (5-FU-HAGS) were investigated. RESULTS: 5-FU-HAGS (hemostatic absorbable gelatin sponge loaded with 5-fluorouracil) was successfully produced with controlled release of the content and was reproducibly suitable for local tumor treatment as an implant to stop bleeding. The encapsulation efficiency of 5-FU-HAGS was above 98%. The in vitro 5-FU release kinetic profile matched a near zero-order equation for 20 days. The in vivo 5-FU plasma concentration was at a more stable level than when 5-FU solution was administered by subcutaneous injection. Bleeding can be stopped more effectively by coating a piece of blank gelatin sponge. The survival ratio of tumor-bearing mice using a 5-FU-HAGS subcutaneous implant was higher when compared to mice given a subcutaneous injection of 5-FU solution. CONCLUSION: The 5-FU-HAGS system is a potential and effective way of enhancing the survival ratio and improving the quality of life of tumor-bearing mice.

Preliminary study on dental pulp stem cell-mediated pulp regeneration in canine immature permanent teeth.

INTRODUCTION: The health of human teeth depends on the integrity of the hard tissue and the activity of the pulp and periodontal tissues, which are responsible for nutritional supply. Without the nourishing of the pulp tissue, the possibility of tooth fracture can increase. In immature permanent teeth, root development may be influenced as well. This study explored the potential of using autologous dental pulp stem cells (DPSCs) to achieve pulp regeneration in a canine pulpless model. METHODS: The establishment of the pulpless animal model involved pulp extirpation and root canal preparation of young permanent incisor teeth in beagles. Autologous DPSCs were obtained from extracted first molars and expanded ex vivo to obtain a larger number of cells. The biological characteristics of canine DPSCs (cDPSCs) were analyzed both in vitro and in vivo by using the same method as used in human DPSCs. cDPSCs were transplanted into the pulpless root canal with Gelfoam as the scaffold, and root development was evaluated by radiographic and histologic analyses. RESULTS: cDPSCs with rapid proliferation, multiple differentiation capacity, and development potential were successfully isolated and identified both in vitro and in vivo. After they were transplanted into the pulpless root canal with Gelfoam as the scaffold, DPSCs were capable of generating pulp-like tissues containing blood vessels and dentin-like tissue. Thickening of the root canal wall was also observed. CONCLUSIONS: This study demonstrates the feasibility of using stem cell-mediated tissue engineering to realize pulp regeneration in immature teeth.

Surgical ventricular restoration with a cell- and cytokine-seeded biodegradable scaffold.

Late after a myocardial infarction (MI), surgical ventricular restoration (SVR) can reduce left ventricular volumes, but an enhanced cardiac patch may be required to restore function. We developed a new, biodegradable patch (modified gelfoam, MGF) consisting of a spongy inner core (gelfoam) to encourage cell engraftment and an outer coating (poly epsilon-caprolactone) to provide sufficient strength to permit ventricular repair. Two weeks after coronary ligation in rats, SVR was performed using one of the following: gelfoam, MGF, MGF patches with hydrogel alone, or with hydrogel and cytokines (stem cell factor, stromal cell-derived factor-1alpha), bone marrow mesenchymal stem cells, or both. Cardiac function and morphology were evaluated by echocardiography, conduction catheterization, magnetic resonance imaging, and histology. Animals whose hearts were repaired with untreated gelfoam died of ventricular rupture. The MGF groups had significantly improved myocardial systolic function vs. MI controls. Enhancement with cytokines and/or cells promoted more alpha-smooth muscle actin-positive cells, more capillaries, greater wall thickness, a more ellipsoid shape, greater fractional shortening, and better-preserved systolic elastance than MGF alone. This combination of the new, reinforced, biodegradable biomaterial and cytokine/cell treatment created a viable tissue after SVR and produced better functional outcomes than un-reinforced gelfoam or MGF alone.

Phase I clinical trial of an adenovirus/prostate-specific antigen vaccine for prostate cancer: safety and immunologic results.

PURPOSE: We performed a phase I clinical trial of adenovirus/prostate-specific antigen (PSA) vaccine in men with measurable metastatic hormone-refractory disease. EXPERIMENTAL DESIGN: Men with measurable metastatic disease received one vaccine injection. Toxicity, immune responses, changes in PSA doubling times, and patient survival were assessed. Thirty-two patients with hormone-refractory metastatic prostate cancer were treated with a single s.c. vaccine injection at one of three dose levels, either as an aqueous solution or suspended in a Gelfoam matrix. All patients returned for physical and clinical chemistry examinations at regular intervals up to 12 months after injections. RESULTS: The vaccine was deemed safe at all doses in both administration forms. There were no serious vaccine-related adverse events; the most prevalent were localized erythema/ecchymoses and cold/flu-like symptoms. Anti-PSA antibodies were produced by 34% of patients and anti-PSA T-cell responses were produced by 68%. PSA doubling time was increased in 48%, whereas 55% survived longer than predicted by the Halabi nomogram. CONCLUSIONS: The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies.

Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin.