Adipose mesenchymal stem cells associated with xenograft in a guided bone regeneration model: a histomorphometric study in rabbit calvaria.

PURPOSE: In spite of their osteoconductive potential, the biomaterials used as substitutes for an autologous graft do not show osteoinductive or osteogenic potential. This study evaluated the association of adult mesenchymal stem cells derived from adipose tissue with xenogenic bone graft in bone regeneration in rabbit calvaria. MATERIALS AND METHODS: Mesenchymal stem cells were harvested from adipose tissue from 12 animals. These cells, combined with hydroxyapatite, were implanted in 12-mm bilateral bone defects created in the calvaria of six rabbits (test group [TG]), whereas only hydroxyapatite was implanted in the defects created in another group of six animals (control group [CG]). One grafted side of each animal was covered by a collagen membrane. After 8 weeks, the animals were sacrificed, and the region of the bone defects was removed and evaluated using histomorphometry and immunohistochemistry. RESULTS: The TG showed higher amounts (P < .05) of vital mineralized tissue and nonvital mineralized tissue, 28.24% ± 6.17% and 27.79% ± 2.72%, respectively, compared with the CG, 13.06% ± 5.24% and 13.52% ± 3.00%, respectively. In TG, no difference was observed (P < .05) in the amount of mineralized tissue between the side that was covered by the membrane vs the side without membrane coverage. On the other hand, a statistically significant difference (P < .05) was observed in the CG with regard to the amount of mineralized tissue between the sides with and without membrane coverage. CONCLUSION: These observations suggest that the association of mesenchymal stem cells derived from adipose tissue with a xenogenic bone graft was capable of promoting better bone regeneration compared with the use of a xenograft alone. Use of a membrane did not produce an increase in the regenerative potential for the TG, in contrast to the CG.

Repair of critical-size bone defects using bone marrow stem cells or autogenous bone with or without collagen membrane: a histomorphometric study in rabbit calvaria.

PURPOSE: The aim of this study was to evaluate bone healing after the use of a xenograft scaffold enriched with bone marrow mesenchymal stem cells (BM-MSCs), an autogenous bone graft, or the scaffold without BM-MSCs. MATERIALS AND METHODS: Eighteen rabbits were used for this study; bilateral 12-mm-diameter defects were created in the animals' parietal bones. The bilateral defects were filled with a xenograft enriched with BM-MSCs (test group [TG]), with autogenous bone graft (positive control group [PCG]), or with a xenograft alone (negative control group [NCG]). In all groups, randomly, one defect was covered with a collagen membrane. The rabbits were sacrificed 8 weeks after surgery, and their parietal bones were harvested and analyzed histomorphometrically. RESULTS: Within the PCG and the NCG, the defects covered with the barrier membrane showed better bone healing. In the TG, the defects covered with the barrier membrane did not show better bone healing (intragroup comparisons by Wilcoxon and Friedman tests for paired data). TG showed percentage of mineralized tissue (MT) of 56.03% ± 3.49% with membrane and 57.71% ± 5.31% without membrane. PCG showed MT of 55.13% ± 4.83% and 49.69% ± 3.81% with and without membrane, respectively, and NCG showed MT of 26.77% ± 7.29% and 19.67% ± 2.66% with and without membrane, respectively. CONCLUSION: Both autogenous bone graft and a xenograft enriched with BM-MSCs were equally effective for bone reconstruction and better than the xenograft alone. The use of a barrier membrane seemed to have a synergistic effect on bone healing in PCG and NCG but not in TG.

Repair of critical-size bone defects using bone marrow stromal cells: a histomorphometric study in rabbit calvaria. Part I: use of fresh bone marrow or bone marrow mononuclear fraction.

OBJECTIVES: The aim of this study was to compare the bone healing observed after the use of (1) a scaffold enriched with fresh bone marrow, (2) a scaffold enriched with bone marrow mononuclear fraction, and (3) a scaffold alone. MATERIAL AND METHODS: Twenty one rabbits were randomly divided into three groups of six animals and 1 group of 3 animals. Bilateral 12-mm diameter defects were created in the animals' parietal bones. In Control Group, the defects were filled with a xenograft alone (n = 6); in Group 1, with a xenograft enriched with fresh bone marrow (n = 6); in Group 2, with a xenograft enriched with bone marrow mononuclear fraction (n = 6) and in Unfilled Group, nothing was grafted (n = 3). In Groups 1, 2, and Control, one of the calvarial defects was randomly covered with a barrier membrane. The rabbits were sacrificed 8 weeks after surgery, and their parietal bones were harvested and analyzed histomorphometrically. RESULTS: The histomorphometric analysis showed no difference between Group 1 and the Control Group regarding non-vital mineralized tissue area, but Group 2 showed a statistically significant higher percentage than the Control Group (P < 0.05) for both situations, with membrane (21.24 ± 3.78% and 13.52 ± 3.00%, respectively) and without membrane (20.91 ± 2.01% and 13.08 ± 1.72%, respectively). Group 2 showed the highest percentage of vital mineralized tissue area, followed by Group 1 and the Control Group (P < 0.05) for both situations, with membrane (28.17 ± 3.19%; 21.14 ± 7.38% and 13.06 ± 5.24%, respectively) and without membrane (21.13 ± 0.55%; 12.45 ± 6.34% and 6.56 ± 1.20%, respectively). Group 2 showed the lowest percentage of non-mineralized tissue area, followed by Group 1 and Control Group (P < 0.05) for both situations, with membrane (50.59 ± 6.64%; 58.75 ± 7.14% and 73.41 ± 6.87%, respectively) and without membrane (57.97 ± 1.91%; 71.74 ± 6.63% and 80.37 ± 2.67%, respectively). The sides in which the defects were covered with the barrier membrane showed better bone healing compared with the uncovered sides, in all groups (intragroup comparison, P < 0.05). The Unfilled Group specimens showed no bone formation. CONCLUSIONS: Both methods using bone marrow stromal cells contributed to enhancing bone healing, especially that using the bone marrow mononuclear fraction. The use of a barrier membrane seemed to have a synergistic effect.

Terapia celular em regeneração óssea. Avaliação histomorfométrica de diferentes metodologias / Cell therapy on bone regeneration. An histomorphometric evaluation of different methodologies

Proposição: este estudo analisou a associação de diferentes metodologias de terapia celular a um enxerto ósseo xenógeno (Bio-Oss). Material e Métodos: 33 coelhos Nova Zelândia foram divididos, randomicamente, em cinco grupos experimentais (n=6) e um grupo controle (n=3). Foram criadas situações de defeitos ósseos bilaterais com o auxílio de fresas trefinas com 12 mm de diâmetro preenchidos – no grupo 1 com Bio-Oss; no grupo 2 com Bio-Oss enriquecido com medula óssea fresca; no grupo 3 com Bio-Oss enriquecido com a fração de células mononucleares da medula óssea; no grupo 4 com Bio-Oss enriquecido com células-tronco mesenquimais da medula óssea; e no grupo 5 com Bio-Oss enriquecido com células-tronco mesenquimais do tecido adiposo. Em cada animal, um dos defeitos ósseos foi recoberto com uma membrana colágena e o outro foi mantido sem recobrimento. Após oito semanas, os animais foram sacrificados, sendo seus ossos parietais fixados em formol 10% e processados para análise histomorfométrica. Resultados: no grupo-controle não existiu formação óssea. A histomorfometria demonstrou, para os lados sem recobrimento por membrana nos grupos de 1 a 5, TMV de 6,56 + 1,20%; 12,45 + 11,65%; 21,13 + 0,55; 27,9 + 5,79 e 16,67 + 5,0; respectivamente. O TMV para os lados com recobrimento pela membrana, nos grupos de 1 a 5, foi de 13,06 + 5,24%; 21,14 + 7,38%; 28,17 + 3,19; 28,24 + 6,17 e 17,21 + 7,3; respectivamente. Conclusão: a terapia celular pode maximizar os resultados regenerativos, normalmente propiciados por um biomaterial osseocondutor. O uso do concentrado de células mononucleares da medula óssea pareceu ser a metodologia com maior potencial para uso clínico.

Objective: this study investigated the combination of different cell therapy approaches in combination with a xenograft (Bio-Oss). Material and Methods: 33 New Zealand rabbits were randomly divided into five experimental groups (n=6) and one control group (n=3). Bilateral bone defects were created using 12 mm diameter trefin burs filled – in group 1, with Bio-Oss, in group 2 with Bio-Oss enriched with fresh bone marrow, in group 3 with Bio-Oss enriched with bone marrow mononuclear fraction, in group 4 with Bio-Oss enriched with bone marrow stem cells and, in group 5, with Bio-Oss enriched with adipose tissue stem cells. In each animal, one bone defect was covered by a collagen membrane and the other defect was not covered. After eight weeks, the animals were sacrificed and their parietal bone fixed in 10% formalin and processed for histomorphometric analysis. Results: in control group bone formation did not occur. Histomorphometry demonstrated, for the sides not covered by the collagen membrane, in groups 1, 2, 3, 4 and 5, a VMT of 6.56 + 1.20%; 12.45 + 11.65%; 21.13 + 0.55; 27.9 + 5.79 and 16.67 + 5.0, respectively. The sides covered by the collagen membrane demonstrated, in groups 1, 2, 3, 4 and 5, a VMT of 13.06 + 5.24%; 21.14 + 7.38%; 28.17 + 3.19; 28.24 + 6.17 and 17.21 + 7.3, respectively. Conclusion: cell therapy can maximize the regenerative results normally obtained by an osseoconductor biomaterial. The use of bone marrow mononuclear fraction concentration seems to be the methodology with higher potential for clinical use

Metástase de adenocarcinoma de cólon para região selar: relato de caso / Metastatic colonic adenocarcinoma from sellar region: case report

A hipófise e a região selar podem ser acometidas por uma série de tumores. Nesse contexto, metástase é um diagnóstico diferencial raro, porém plausível. O diagnóstico de metástase para região selar é desafiador. Assim, espessamento da haste hipofisária, invasão de seio cavernoso e esclerose ao redor da sela são detalhes sutis que, apesar de não serem conclusivos, podem sugerir esse diagnóstico. Neste artigo os autores descrevem um caso de um paciente sem antecedentes oncológicos e com RM e TC sugestivas de macroadenoma hipofisário. Inesperadamente, a lesão era um adenocarcinoma metastático de cólon. Metástases cerebrais de câncer colorretal são raras, principalmente para região selar e normalmente aparecem após o diagnóstico da lesão primária. Nosso objetivo é descrever um caso de metástase de cólon para região selar e sua evolução e rever dados de literatura.

The pituitary gland and sellar region may be a site for a number of tumors. In this context a rare but feasible differential diagnosis is metastasis. The diagnosis of metastasis in the sellar region is challenging. Therefore, thickening of the pituitary stalk, invasion of the cavernous sinus and sclerosis around the sella, although not conclusive, may suggest this diagnosis. In this article the authors describe a case of a patient without any oncological history and with MRI and CT-scan suggestive of pituitary macroadenoma. Surprisingly the tumor was an metastatic colonic adenocarcinoma. Colonic and rectal metastasis to the brain are rare, particularly to the sellar region and normally appear after the primary lesion is already diagnosed. Our goal is to describe a case of colonic metastasis to the sellar region and its evolution and review literature data.