We show that human embryonic stem cell-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine-lesioned rat striatum and, in combination with the cells newly differentiated from their progenitors, contributed to locomotive function recovery at 5 months. The animal behavioral improvement was correlated with the dopamine neurons present in the graft. Although the donor cells contained forebrain and midbrain dopamine neurons, the dopamine neurons present in the graft mainly exhibited a midbrain, or nigra, phenotype, suggesting the importance of midbrain dopamine neurons in functional repair. Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain.
Objectives/Hypothesis: Design and test a novel biomaterial for injection laryngoplasty aimed to increase the duration of effectiveness of micronized acellular dermis.Study Design: Animal model. Methods: Injection laryngoplasty was performed in three groups (n 5 5) of New Zealand White rabbits. Acellular dermis was either used alone as a control (group 1), was combined with undifferentiated stem cells (group 2), or with predifferentiated chondrocytic cells (group 3). Groups 2 and 3 were supplemented with growth factors. Animals were sacrificed 4 and 12 weeks after laryngoplasty and histologic analysis was completed. The major outcome measure was volume of tissue remaining.Results: After 4 weeks, the mean volume of tissue remaining was 341 6 89 mm 3 , 295 6 102 mm 3 , and 133 6 15 mm 3 , for groups 1 to 3, respectively. At the 12-week time point, volumes were 62 6 62 mm 3 , 235 6 35 mm 3 , and 107 6 99 mm 3 . After 12 weeks, there was a significantly higher volume in group 2 compared to group 1 or 3 (P 5 .01, P 5 .04). Volumes between week 4 and week 12 were significantly lower in group 1 (P 5 .02), but not significantly different for groups 2 and 3 (P 5 .38, P 5 .74). Histologic evaluation revealed a robust lymphocytic infiltration in all cases as well as morphologic and immunophenotypic features suggestive of chondrogenic differentiation in a single animal.Conclusions: Micronized acellular dermis combined with stem cells and growth factors showed significantly less resorption 12 weeks after injection laryngoplasty compared to micronized acellular dermis alone. Groups using novel tissue-engineered biomaterial showed a lower resorption rate over time compared with acellular dermis alone.
Objectives/Hypothesis: Test a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice.Study Design: Animal model. Methods: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross-linked jellyfish collagen (MX-JC) and adipose derived stem cells (ADSCs), Group 2, MX-JC alone, Group 3, cross-linked hyaluronic acid (X-HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology.Results: After 100 μL IL MRI volumes (means AE STD) at 4 and 12 weeks were:
Report two positive sentinel node biopsies for sinonasal melanoma. Retrospective review. Academic tertiary care center. Patients who underwent sentinel node biopsy for sinonasal melanoma between November 1, 2014 and November 1, 2015. Clinical course. Two patients were identified. Patient 1 (83M) presented with a sinonasal melanoma anterior to the left inferior turbinate and was clinically N0 neck. Lymphoscintigraphy revealed two sentinel nodes in the ipsilateral and three in the contralateral cervical basins. The left level I sentinel node was positive for melanoma and lymphadenectomy showed no additional metastases. Patient 2 (71F) presented after incomplete resection of a sinonasal melanoma of the left posterior maxillary sinus wall and was clinically N0 neck. Lymphoscintigraphy with single-photon emission computed tomography (SPECT/CT) localization revealed one sentinel node in the parapharyngeal space and another in the ipsilateral cervical basin. Metastatic melanoma was found in both nodes and completion lymphadenectomy was negative for additional disease. Both patients developed distant metastasis in less than 1 year after surgical resection but responded well to adjuvant immunomodulatory chemotherapeutic agents. Sentinel node biopsy for sinonasal melanoma can provide crucial clinical evidence of regional metastasis prior to overt clinical signs and symptoms. This intraoperative tool has the potential to improve detection of regional metastasis and improve long-term outcomes of this aggressive malignancy.
The osseointegration of long‐term implants is often incomplete such that gaps remain between the implant surface and the surrounding hard tissue. This study examines the effect of soluble recombinant human bone morphogenic protein 2 (rhBMP‐2) on gap healing and osseous integration. The effect of a single, intraoperative application of soluble rhBMP‐2 on the formation of new bone around titanium implants was studied. A total of 8 titanium‐alloy cylinders (Ti‐6Al‐4V) with a plasma spray coating (TPS; 400 μm thickness) were implanted into femoral condyles of mature sheep: rhBMP‐2 solution (1 μg) was pipetted into the 1 mm wide cleft around 4 implants; 4 further implants served as rhBMP‐2‐free controls. Two of these controls exhibited an additional calciumphosphate‐coating. The cleft around the implants served as testing zone to study the formation of new bone by microradiographical and histological analyses. The follow‐up periods were 4 and 9 weeks, respectively. A significant amount of new bone contacting the implants' surface was detected where rhBMP‐2‐solution had been used: In 50% a circumferential osseoinduction occurred within 4 weeks and a nearly complete osseointegration was observed after 9 weeks. In all cases bone formation was exaggerated and filled the spongiosa with compact bone. Time matched TPS‐controls and controls with calciumphosphate coating showed no notable formation of new bone. The results suggest that a single administration of soluble rhBMP‐2 into a bone cavity can augment bone formation and also osseointegration of titanium implants. Further investigations based on these findings are necessary to develop long‐term implants (e. g. joint replacements) with rhBMP‐2‐biocoating for humans.
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