Cell therapy with adipose tissue-derived human stem cells in the urinary bladder improves detrusor contractility and reduces voiding residue / A terapia celular com células-tronco humanas derivadas do tecido adiposo na bexiga urinária melhora a contratilidade do detrusor e reduz o resíduo miccional

Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.

A Hipocontratilidade Detrusora (HD) é uma doença sem um tratamento padrão-ouro na medicina tradicional. Logo, há a necessidade de desenvolvimento de terapias inovadoras. O presente relato apresenta um caso de paciente com HD transplantado duas vezes com 2 x 106 células-tronco mesenquimais derivadas do tecido adiposo que obteve melhoras significativas em sua qualidade de vida. Os resultados demonstraram que a terapia celular reduziu o resíduo miccional de 1.800mL para 800mL; a Capacidade Cistométrica Máxima de 800 para 550mL; a complacência de 77 para 36,6mL/cmH2O. A terapia celular também aumentou o fluxo máximo de 3 para 11mL/s; a pressão detrusora de 08 para 35cmH2O; o volume urinado de 267 para 524mL e o índice de contratilidade vesical (BCI) de 23 para 90. O score do International Continence on Incontinence Questionare - Short Form passou de 17 para 8. Diante do exposto, infere-se que o transplante de células-tronco mesenquimais derivadas do tecido adiposo é uma estratégia terapêutica inovadora e eficiente para o tratamento da HD e para melhoria da qualidade de vida de pacientes acometidos por essa doença.

Dantrolene e células-tronco mesenquimais promovem melhora funcional em ratos Wistar com trauma espinhal agudo / Dantrolene and mesenchymal stem cells promote functional improvement in Wistar rats with spinal cord injury

Objetivou-se avaliar o efeito do dantrolene (DAN) e das células-tronco mesenquimais (CTM) no trauma espinhal agudo (TEA). Sessenta ratos Wistar foram divididos nos grupos CTM, DAN + CTM, DAN, trauma e placebo (TP) e sem trauma e placebo (STP). Realizou-se laminectomia de T12 em todos os grupos, seguida de TEA contusivo ∕ compressivo, com exceção do grupo STP. Uma hora depois, os grupos DAN + CTM e DAN receberam 10mg/kg de DAN. Após sete dias os grupos CTM e DAN + CTM receberam 1x106 células, por via intravenosa. Testes comportamentais foram realizados para avaliar a recuperação funcional durante 28 dias. Os animais traumatizados apresentaram paraplegia. Houve melhora funcional significativa nos grupos tratados com CTM, DAN ou associação DAN + CTM em comparação ao grupo TP (p<0,05). Conclui-se que o DAN e as CTM para tratamento de TEA em ratos apresentam efeitos neuroprotetores e promovem melhora neurológica funcional.(AU)

This study aimed to evaluate the effects of dantrolene (DAN) and mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI). Sixty Wistar rats were divided into groups MSCs, MSCs + DAN, DAN, trauma and placebo (TP) and no trauma and placebo (STP). Laminectomy was performed at T12 level in all animals, followed by a weight-drop model of SCI, except for the STP group. An hour later, the MSCs + DAN and DAN groups received 10mg/kg of DAN. After seven days, the MSCs and MSCs + DAN groups received 1x106 cells intravenously. Behavioral tests were performed to assess functional recovery for 28 days. Traumatized animals showed paraplegia. There was a significant improvement in groups MSCs, DAN and MSCs + DAN compared to TP (p<0.05). It was concluded that DAN and MSCs for the treatment of SCI in rats have neuroprotection effect and promote functional neurological improvement.(AU)

Expression patterns of mesenchymal stem cell-specific proteins in adipose tissue-derived cells: possible immunosuppressing agent in partial allograft for restoring the urinary bladder in rabbits / Padrão de expressão de proteínas específicas das células-tronco mesenquimais derivadas de tecido adiposo: possível agente imunossupressor em aloenxerto parcial para restauração de vesícula urinária de coelhos

Adipose tissue-derived stem cells (ADSCs) are an attractive source of mesenchymal stem cells (MSCs) for use in tissue engineering and clinical applications. This paper focuses on the characterization of ADSCs used as immunosuppressive agent in rabbits undergoing partial allograft for urine bladder restorage. For this study highlighted the characterization of the ADSCs used as immunosuppressive agents in rabbits submitted to partial allograft for restoration of the urinary vesicle, using 25 animals, six months old, New Zealand. ADSCs at the third peal were characterized by the MSC-specific CD105, CD73 and CD90 expression and by the absence of the hematopoietic marker CD45, as revealed by flow cytometry analysis. Moreover, ADSCs were efficient in preventing allograft rejection from the urinary bladder, as judged by biochemical, clinical and ultrasonography analysis. Together, these results compose characterization of protein expression profiles and immunosuppressive functionality of ADSCs in rabbits, which had undergone partial allografts of the urinary bladder, foreseeing future applications in clinical practice.(AU)

As células mesenquimais derivadas de tecido adiposo (ADSCs) são uma fonte atraente de células-tronco mesenquimais (MSCs) para uso na engenharia de tecidos e suas aplicações clínicas. Este trabalho destacou a caracterização das ADSCs utilizadas como agentes imunossupressores em coelhos submetidos a aloenxerto parcial para restauração da vesícula urinária, sendo utilizados 25 animais, de seis meses de idade, Nova Zelândia. As ADSCs, após o terceiro repique, foram caracterizadas pela expressão específica de MSC CD105, CD73 e CD90 e pela ausência do marcador hematopoiético CD45, tal como revelado por análise de citometria de fluxo. Além disso, os ADSCs foram eficientes na prevenção da rejeição de aloenxertos da vesícula urinária, conforme avaliado por análises clínica, bioquímica e ultrassonográfica. Juntos, esses resultados compõem a caracterização dos perfis de expressão proteica e a funcionalidade imunossupressora de ADSCs em coelhos, que sofreram aloenxertos parciais da bexiga, prevendo futuras aplicações na prática clínica.(AU)

Dantrolene e células-tronco mesenquimais promovem melhora funcional em ratos Wistar com trauma espinhal agudo / Dantrolene and mesenchymal stem cells promote functional improvement in Wistar rats with spinal cord injury

Objetivou-se avaliar o efeito do dantrolene (DAN) e das células-tronco mesenquimais (CTM) no trauma espinhal agudo (TEA). Sessenta ratos Wistar foram divididos nos grupos CTM, DAN + CTM, DAN, trauma e placebo (TP) e sem trauma e placebo (STP). Realizou-se laminectomia de T12 em todos os grupos, seguida de TEA contusivo ∕ compressivo, com exceção do grupo STP. Uma hora depois, os grupos DAN + CTM e DAN receberam 10mg/kg de DAN. Após sete dias os grupos CTM e DAN + CTM receberam 1x106 células, por via intravenosa. Testes comportamentais foram realizados para avaliar a recuperação funcional durante 28 dias. Os animais traumatizados apresentaram paraplegia. Houve melhora funcional significativa nos grupos tratados com CTM, DAN ou associação DAN + CTM em comparação ao grupo TP (p<0,05). Conclui-se que o DAN e as CTM para tratamento de TEA em ratos apresentam efeitos neuroprotetores e promovem melhora neurológica funcional.(AU)

This study aimed to evaluate the effects of dantrolene (DAN) and mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI). Sixty Wistar rats were divided into groups MSCs, MSCs + DAN, DAN, trauma and placebo (TP) and no trauma and placebo (STP). Laminectomy was performed at T12 level in all animals, followed by a weight-drop model of SCI, except for the STP group. An hour later, the MSCs + DAN and DAN groups received 10mg/kg of DAN. After seven days, the MSCs and MSCs + DAN groups received 1x106 cells intravenously. Behavioral tests were performed to assess functional recovery for 28 days. Traumatized animals showed paraplegia. There was a significant improvement in groups MSCs, DAN and MSCs + DAN compared to TP (p<0.05). It was concluded that DAN and MSCs for the treatment of SCI in rats have neuroprotection effect and promote functional neurological improvement.(AU)

Expression patterns of mesenchymal stem cell-specific proteins in adipose tissue-derived cells: possible immunosuppressing agent in partial allograft for restoring the urinary bladder in rabbits / Padrão de expressão de proteínas específicas das células-tronco mesenquimais derivadas de tecido adiposo: possível agente imunossupressor em aloenxerto parcial para restauração de vesícula urinária de coelhos

Adipose tissue-derived stem cells (ADSCs) are an attractive source of mesenchymal stem cells (MSCs) for use in tissue engineering and clinical applications. This paper focuses on the characterization of ADSCs used as immunosuppressive agent in rabbits undergoing partial allograft for urine bladder restorage. For this study highlighted the characterization of the ADSCs used as immunosuppressive agents in rabbits submitted to partial allograft for restoration of the urinary vesicle, using 25 animals, six months old, New Zealand. ADSCs at the third peal were characterized by the MSC-specific CD105, CD73 and CD90 expression and by the absence of the hematopoietic marker CD45, as revealed by flow cytometry analysis. Moreover, ADSCs were efficient in preventing allograft rejection from the urinary bladder, as judged by biochemical, clinical and ultrasonography analysis. Together, these results compose characterization of protein expression profiles and immunosuppressive functionality of ADSCs in rabbits, which had undergone partial allografts of the urinary bladder, foreseeing future applications in clinical practice.(AU)

As células mesenquimais derivadas de tecido adiposo (ADSCs) são uma fonte atraente de células-tronco mesenquimais (MSCs) para uso na engenharia de tecidos e suas aplicações clínicas. Este trabalho destacou a caracterização das ADSCs utilizadas como agentes imunossupressores em coelhos submetidos a aloenxerto parcial para restauração da vesícula urinária, sendo utilizados 25 animais, de seis meses de idade, Nova Zelândia. As ADSCs, após o terceiro repique, foram caracterizadas pela expressão específica de MSC CD105, CD73 e CD90 e pela ausência do marcador hematopoiético CD45, tal como revelado por análise de citometria de fluxo. Além disso, os ADSCs foram eficientes na prevenção da rejeição de aloenxertos da vesícula urinária, conforme avaliado por análises clínica, bioquímica e ultrassonográfica. Juntos, esses resultados compõem a caracterização dos perfis de expressão proteica e a funcionalidade imunossupressora de ADSCs em coelhos, que sofreram aloenxertos parciais da bexiga, prevendo futuras aplicações na prática clínica.(AU)

Dantrolene e células-tronco mesenquimais promovem melhora funcional em ratos Wistar com trauma espinhal agudo

ABSTRACT: This study aimed to evaluate the effects of dantrolene (DAN) and mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI). Sixty Wistar rats were divided into groups MSCs, MSCs + DAN, DAN, trauma and placebo (TP) and no trauma and placebo (STP). Laminectomy was performed at T12 level in all animals, followed by a weight-drop model of SCI, except for the STP group. An hour later, the MSCs + DAN and DAN groups received 10mg/kg of DAN. After seven days, the MSCs and MSCs + DAN groups received 1x106 cells intravenously. Behavioral tests were performed to assess functional recovery for 28 days. Traumatized animals showed paraplegia. There was a significant improvement in groups MSCs, DAN and MSCs + DAN compared to TP (p 0.05). It was concluded that DAN and MSCs for the treatment of SCI in rats have neuroprotection effect and promote functional neurological improvement.

RESUMO: Objetivou-se avaliar o efeito do dantrolene (DAN) e das células-tronco mesenquimais (CTM) no trauma espinhal agudo (TEA). Sessenta ratos Wistar foram divididos nos grupos CTM, DAN + CTM, DAN, trauma e placebo (TP) e sem trauma e placebo (STP). Realizou-se laminectomia de T12 em todos os grupos, seguida de TEA contusivo compressivo, com exceção do grupo STP. Uma hora depois, os grupos DAN + CTM e DAN receberam 10mg/kg de DAN. Após sete dias os grupos CTM e DAN + CTM receberam 1x106 células, por via intravenosa. Testes comportamentais foram realizados para avaliar a recuperação funcional durante 28 dias. Os animais traumatizados apresentaram paraplegia. Houve melhora funcional significativa nos grupos tratados com CTM, DAN ou associação DAN + CTM em comparação ao grupo TP (p 0,05). Conclui-se que o DAN e as CTM para tratamento de TEA em ratos apresentam efeitos neuroprotetores e promovem melhora neurológica funcional.

Minimally Invasive Approach to Renal Artery Using Different Types of Catheter by Conventional Radiology

Background: Several routes of administration have been used for cell and gene therapy delivery in kidney disease in the last years. Moreover, a more homogenous distribution and a higher response was observed when administered intra-arterially. The main objective of the present study was to describe and to compare the use of Fogarty thru-lumen embolectomy catheter with angiographic catheter through the femoral artery by using conventional radiology as a guide.Materials, Methods & Results: Seven healthy dogs were used in these experiments. First, a Fogarty thru-lumen embolectomy catheter was introduced followed by an angiographic catheter. The primary outcome was the number of attempts for the placement of the introducer and the number of radiographic studies to carry out nephrography. Preceding the surgical procedure, ultrasonographic evaluation was performed in all animals in order to measure the diameter of the left and right femoral arteries, left and right renal and abdominal aorta at the renal level. After trichotomy and antisepsis of the medial face of the two pelvic limbs, the 6F valve introducer was placed based on the modified Seldinger technique. Thereafter, aortography was performed, showing its collateral arteries, with contrast injection, and it was estimated how much of the Fogarty 5,5F catheter had to be introduced. Subsequently, a guidewire was inserted throu

Acesso minimamente invasivo da artéria renal com diferentes tipos de cateteres por radiologia convencional / Minimally invasive approach to renal artery using different types of catheter by conventional radiology

Background: Several routes of administration have been used for cell and gene therapy delivery in kidney disease in the last years. Moreover, a more homogenous distribution and a higher response was observed when administered intra-arterially. The main objective of the present study was to describe and to compare the use of Fogarty thru-lumen embolectomy catheter with angiographic catheter through the femoral artery by using conventional radiology as a guide.Materials, Methods & Results: Seven healthy dogs were used in these experiments. First, a Fogarty thru-lumen embolectomy catheter was introduced followed by an angiographic catheter. The primary outcome was the number of attempts for the placement of the introducer and the number of radiographic studies to carry out nephrography. Preceding the surgical procedure, ultrasonographic evaluation was performed in all animals in order to measure the diameter of the left and right femoral arteries, left and right renal and abdominal aorta at the renal level. After trichotomy and antisepsis of the medial face of the two pelvic limbs, the 6F valve introducer was placed based on the modified Seldinger technique. Thereafter, aortography was performed, showing its collateral arteries, with contrast injection, and it was estimated how much of the Fogarty 5,5F catheter had to be introduced. Subsequently, a guidewire was inserted through the catheter followed by the Fogarty catheter. Another x-ray was taken to show the position of the catheter. It was observed whether the catheter was positioned correctly and the cuff was filled, and then another contrasting radiograph was performed. If the contrast was not going to the kidneys, the cuff of the catheter was deflated, the catheter was repositioned and a new contrast radiography was performed.[...]

Acesso minimamente invasivo da artéria renal com diferentes tipos de cateteres por radiologia convencional / Minimally invasive approach to renal artery using different types of catheter by conventional radiology

Background: Several routes of administration have been used for cell and gene therapy delivery in kidney disease in the last years. Moreover, a more homogenous distribution and a higher response was observed when administered intra-arterially. The main objective of the present study was to describe and to compare the use of Fogarty thru-lumen embolectomy catheter with angiographic catheter through the femoral artery by using conventional radiology as a guide.Materials, Methods & Results: Seven healthy dogs were used in these experiments. First, a Fogarty thru-lumen embolectomy catheter was introduced followed by an angiographic catheter. The primary outcome was the number of attempts for the placement of the introducer and the number of radiographic studies to carry out nephrography. Preceding the surgical procedure, ultrasonographic evaluation was performed in all animals in order to measure the diameter of the left and right femoral arteries, left and right renal and abdominal aorta at the renal level. After trichotomy and antisepsis of the medial face of the two pelvic limbs, the 6F valve introducer was placed based on the modified Seldinger technique. Thereafter, aortography was performed, showing its collateral arteries, with contrast injection, and it was estimated how much of the Fogarty 5,5F catheter had to be introduced. Subsequently, a guidewire was inserted through the catheter followed by the Fogarty catheter. Another x-ray was taken to show the position of the catheter. It was observed whether the catheter was positioned correctly and the cuff was filled, and then another contrasting radiograph was performed. If the contrast was not going to the kidneys, the cuff of the catheter was deflated, the catheter was repositioned and a new contrast radiography was performed.[...](AU)

Células osteoprogenitoras podem aumentar a formação óssea precoce em defeitos ósseos críticos de cães / Osteoprogenitor cells can enhance early bone formation in critical bone defects in dogs

The aim of this study was to evaluate the effect of osteoprogenitor cells derived from mesenchymal stem cells from adipose tissue (OC-AD-MSCs), and differentiated into osteoblasts, in the treatment of critical bone defects in dogs. Adipose tissue derived mesenchymal stem cells (AD-MSCs) were subjected to osteogenic differentiation for 21 days and used in the treatment of bone defects in dogs radius. Either three experimental groups were bone defects treated with OC-AD-MSCs (OC), defects filled with autogenous bone (Control- C +), or empty defects (Control- C -). Bone regeneration was assessed by radiology, densitometry, and histomorphometry. The area of new bone formation was higher in the OC group compared to the control group (C-) on postoperative day 15. Defects treated with OC-AD-MSCs showed greater neovascularization than the other two groups at 90 days. We concluded that treatment with OC-AD-MSCs increased the area of new bone formation 15 days after surgery; however, it didn’t complete the bone union in critical bone defects in the radius of dogs at 90 days.

O objetivo deste estudo foi avaliar o efeito das células osteoprogenitoras derivadas de células tronco mesenquimais do tecido adiposo (CO-CTM-AD) no tratamento de defeitos ósseos críticos de cães. As células tronco mesenquimais do tecido adiposo (CTM-AD) foram submetidas à diferenciação osteogênica por 21 dias e usadas no tratamento de defeitos ósseos em rádios de cães. Foram constituídos três grupos experimentais: defeitos ósseos tratados com CO-CTM-AD (OC), defeitos preenchidos com osso autógeno (C+) e defeitos não preenchidos (C-). A regeneração óssea foi avaliada por meio de exames radiográficos, densitométricos e histomorfométricos. A área de neoformação óssea foi maior no grupo OC em relação ao grupo C- no 15o dia de pós-operatório. Os defeitos tratados com CO-CTM-AD mostraram maior neovascularização que os demais grupos aos 90 dias de avaliação. Conclui-se que o tratamento com CO-CTM-AD aumentou a área de osso neoformado no 15o dia de pós-operatório, mas não foi suficiente para que houvesse a completa união óssea em defeitos ósseos críticos no rádio de cães aos 90 dias.

Células osteoprogenitoras podem aumentar a formação óssea precoce em defeitos ósseos críticos de cães / Osteoprogenitor cells can enhance early bone formation in critical bone defects in dogs

The aim of this study was to evaluate the effect of osteoprogenitor cells derived from mesenchymal stem cells from adipose tissue (OC-AD-MSCs), and differentiated into osteoblasts, in the treatment of critical bone defects in dogs. Adipose tissue derived mesenchymal stem cells (AD-MSCs) were subjected to osteogenic differentiation for 21 days and used in the treatment of bone defects in dogs radius. Either three experimental groups were bone defects treated with OC-AD-MSCs (OC), defects filled with autogenous bone (Control- C +), or empty defects (Control- C -). Bone regeneration was assessed by radiology, densitometry, and histomorphometry. The area of new bone formation was higher in the OC group compared to the control group (C-) on postoperative day 15. Defects treated with OC-AD-MSCs showed greater neovascularization than the other two groups at 90 days. We concluded that treatment with OC-AD-MSCs increased the area of new bone formation 15 days after surgery; however, it didnt complete the bone union in critical bone defects in the radius of dogs at 90 days.(AU)

O objetivo deste estudo foi avaliar o efeito das células osteoprogenitoras derivadas de células tronco mesenquimais do tecido adiposo (CO-CTM-AD) no tratamento de defeitos ósseos críticos de cães. As células tronco mesenquimais do tecido adiposo (CTM-AD) foram submetidas à diferenciação osteogênica por 21 dias e usadas no tratamento de defeitos ósseos em rádios de cães. Foram constituídos três grupos experimentais: defeitos ósseos tratados com CO-CTM-AD (OC), defeitos preenchidos com osso autógeno (C+) e defeitos não preenchidos (C-). A regeneração óssea foi avaliada por meio de exames radiográficos, densitométricos e histomorfométricos. A área de neoformação óssea foi maior no grupo OC em relação ao grupo C- no 15o dia de pós-operatório. Os defeitos tratados com CO-CTM-AD mostraram maior neovascularização que os demais grupos aos 90 dias de avaliação. Conclui-se que o tratamento com CO-CTM-AD aumentou a área de osso neoformado no 15o dia de pós-operatório, mas não foi suficiente para que houvesse a completa união óssea em defeitos ósseos críticos no rádio de cães aos 90 dias.(AU)

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats / Células-tronco mesenquimais ampliam a resposta de células-tronco neurais endógenas no trauma da medula espinhal em ratos

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.(AU)

A lesão medular resulta em déficits neurológicos graves, a maioria irreversíveis. A terapia celular representa uma estratégia para o tratamento, especialmente com a utilização de células-tronco, com resultados satisfatórios em vários modelos experimentais. O objetivo do estudo foi comparar o tratamento de lesões da medula espinal (SCI), com e sem o uso de células-tronco mesenquimais (MSC), para investigar se as MSCs migram e/ou permanecem no local de lesão, e para analisar os efeitos de MSCs sobre a inflamação, reatividade astrocitária e ativação das células-tronco endógenas. Três horas depois da SCI, os animais receberam as MSC derivadas da medula óssea (1 × 107 em 1 mL de PBS, IV). Os animais foram sacrificados 24 horas, 7 e 21 dias pós-lesão. As MSC não estavam presentes no local da lesão e a avaliação por imunofluorescência demonstrou atenuação significativa da resposta inflamatória com redução em macrófagos marcados com anticorpo anti CD68 (ED1), diminuição da imunorreatividade de astrócitos (GFAP +) e maior ativação das células-tronco endógenas (nestin+) nos grupos tratados. Assim, o transplante de células teve efeito positivo sobre a recuperação de lesão traumática da medula espinal, possivelmente devido ao potencial das MSCs para atenuar a resposta imunológica.(AU)

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats / Células-tronco mesenquimais ampliam a resposta de células-tronco neurais endógenas no trauma da medula espinhal em ratos

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

A lesão medular resulta em déficits neurológicos graves, a maioria irreversíveis. A terapia celular representa uma estratégia para o tratamento, especialmente com a utilização de células-tronco, com resultados satisfatórios em vários modelos experimentais. O objetivo do estudo foi comparar o tratamento de lesões da medula espinal (SCI), com e sem o uso de células-tronco mesenquimais (MSC), para investigar se as MSCs migram e/ou permanecem no local de lesão, e para analisar os efeitos de MSCs sobre a inflamação, reatividade astrocitária e ativação das células-tronco endógenas. Três horas depois da SCI, os animais receberam as MSC derivadas da medula óssea (1 × 107 em 1 mL de PBS, IV). Os animais foram sacrificados 24 horas, 7 e 21 dias pós-lesão. As MSC não estavam presentes no local da lesão e a avaliação por imunofluorescência demonstrou atenuação significativa da resposta inflamatória com redução em macrófagos marcados com anticorpo anti CD68 (ED1), diminuição da imunorreatividade de astrócitos (GFAP +) e maior ativação das células-tronco endógenas (nestin+) nos grupos tratados. Assim, o transplante de células teve efeito positivo sobre a recuperação de lesão traumática da medula espinal, possivelmente devido ao potencial das MSCs para atenuar a resposta imunológica.

Nested-PCR multiplex test with increased sensitivity for detection of allogeneic cells transplanted from male to female mice / Nested-PCR multiplex com aumento da sensibilidade de detecção de células alogênicas transplantadas de camundongos machos para fêmeas

Cell therapy has shown encouraging perspectives for human and veterinary medicine. Experimentally, genetic manipulation allows to mark and locate allogeneic cells. However, this makes their genotype/phenotype different from non-marked cells used clinically. Alternatively, the presence of the Y-chromosome enables male donor cells detection in female organisms. However, the concentration of engrafted cells may be minimal in tissues, due to systemic distribution. In this study, a nested-PCR multiplex test was developed, aiming to increase the sensitivity of the presence/absence diagnosis of male mice adipose-derived (ADSC-Y) and bone marrow mononuclear (BMNC-Y) cells in samples of blood and lungs from females, after endovenous transplantation. Four females received placebos; four females received ADSC-Y from two males; and four females received BMNC-Y from two males. The PCR first-step included two primer sets (multiplex): one for amplification of a Y-chromosome fragment (SRYout; 300bp); the other for amplification of an X-chromosome (DXNds3 gene) fragment. In the PCR second-step, one primer set (SRYinn) was used for amplification of a 110bp fragment, restrained in the SRYout amplification product. The PCR internal control (DXNds3 gene) was detected in all DNA samples, whereas the SRY gene external fragment (300bp) was detected exclusively in ADSC-Y and BMNC-Y pure DNA samples. The SRY gene internal fragment (110bp) was detected in 100% of the blood and lung samples from the ADSC-Y and BMNC-Y female recipients. The nested-PCR technique increased sensitivity and reliability for molecular diagnostic of presence or absence of male mice cells in body fluids and tissues of female recipients after endovenous transplantation.(AU)

A terapia celular traz perspectivas encorajadoras à medicina humana e veterinária. Experimentalmente, a manipulação genética permite a marcação e a localização de células alogênicas. Porém, isso torna seu genótipo/fenótipo diferente daquelas usadas clinicamente, sem marcação. Alternativamente, a presença do cromossomo Y possibilita detectar células de doadores machos no organismo de fêmeas. Todavia, a concentração de células transplantadas pode ser mínima em certos tecidos, pela distribuição sistêmica. Neste estudo, foi desenvolvida uma nested-PCR multiplex, visando a aumentar a sensibilidade do diagnóstico de presença/ausência de células derivadas do tecido adiposo (CDTA-Y) e derivadas da fração mononuclear da medula óssea (CFMO-Y) de camundongos machos, em amostras de sangue e de pulmões de camundongos fêmeas, após transplante endovenoso. Quatro fêmeas receberam placebo; quatro fêmeas receberam CDTA-Y de dois machos; e quatro fêmeas receberam CFMO-Y de dois machos. A primeira fase da PCR teve dois pares de primers (multiplex): um para amplificação de fragmento do cromossomo Y (SRYout; 300pb); outro para amplificação de fragmento do cromossomo X (gene DXNds3). Na segunda fase da PCR, foi usado um par de primers para amplificação de fragmento de 110pb (SRYinn) interno ao produto amplificado pelo SRYout. O controle interno da reação (gene DXNds3) foi detectado em todas as amostras de DNA testadas, enquanto que o fragmento externo do gene SRY (300pb) foi detectado apenas nas amostras puras de DNA de CDTA-Y e CFMO-Y. O fragmento interno do gene SRY (110pb) foi detectado no sangue e nos pulmões de 100% das receptoras de CDTA-Y e CFMO-Y. A técnica de nested-PCR aumentou a sensibilidade e a segurança do diagnóstico molecular de presença ou ausência de células de camundongos machos em fluidos e tecidos de receptoras fêmeas após transplante endovenoso.(AU)

Cirugías reconstructivas de la vejiga en pequenõs animales: indicaciones y principales técnicas / Reconstructive surgeries of bladder in small animals: indications and main techniques / Cirurgias reconstrutivas da bexiga em pequenos animais: indicações e principais técnicas

Las indicaciones para la cirugía reconstructiva de vejiga son innumeras y abarcan rupturas con laceración tecidual grave, neoplasias, cistitis intersticiales crónicas, disfunciones neurológicas y anormalidades genitourinarias congénitas. La cistotomía se enfoca al tratamiento de varias de esas afecciones. Después de su realización, inicia el proceso de cicatrización tisular en el que se incluye la distención del tejido remanente. El estiramento del tejido vesical ocurre durante algunos meses a partir de la excisión de la pared de la vejiga en hasta un 75% de su extensión. En situaciones en que el área total removida sea super a ese valor se debe recurrir a la recontrucción tisular de la vejiga con el objetivo de garantizar la complacencia vesical. El objetivo de la presente revisión de literatura es describir las principales técnicas para la reconstrucción vesical, ya que su realización es cada vez mas requerida en la rutina clínica y quirúrgica en medicina veterinaria posterior a procedimientos como cistotomia subtotal.(AU)

The indications for repairing surgery of the bladder are numerous and incloses rupture with severe tecidual laceration, neoplasmas, chronic interstitial cystitis, neurological disfunctions and congenital abnormatlities. Cystectomy is used to treat many of these conditions. After its execution, the tecidual cicatrization occurs by the combination of process amongst which, the distension of the remainder tissue. The strechtning of the vesical tissue occurs in several months as long as the excised part does not correspond to more than 75% of its extension. When the removed part is bigger than this, the tecidual reconstruction must be proceeded in order to assure the vesical complacence. The aim of the present work is to describe the main techniques for bladder reconstruction, since its execution its growing frequency in the clinical and surgical routine of veterinary medicine after the subtotal cystectomy.(AU)

As indicações para a cirurgia reparadora da bexiga são inúmeras e abrangem ruptura com laceração tecidual grave, neoplasias, cistites intersticiais crônicas, disfunções neurológicas e anormalidades genitourinárias congênitas. A cistectomia destina-se ao tratamento de diversas dessas afecções. Após a sua realização, a cicatrização tecidual ocorre por meio da combinação de processos dentre os quais, a distenção do tecido remanescente. O alongamento do tecido vesical ocorre em alguns meses desde que excisada a parede da bexiga em até 75% da sua extensão. Nas situações em que a área total removida seja superior a esse valor deve-se recorrer à reconstrução tecidual da bexiga a fim de garantir a complacência vesical. O objetivo da presente revisão de literatura é descrever as principais técnicas para a reconstrução da bexiga, visto sua realização ser cada vez mais requerida na rotina clínica e cirúrgica em Medicina Veterinária após cistectomia subtotal.(AU)

Comparação do potencial condrogênico de células-tronco mesenquimais de líquido sinovial, medula óssea e tecido adiposo de equinos

As células-tronco mesenquimais (CTMs) representam uma terapia promissora no tratamento das enfermidades articulares dos equinos. As características de imunomodulação e possível efeito regenerativo as qualificam para essa finalidade. Entretanto, ainda não foi estabelecida qual fonte de CTMs é a mais indicada para originar estrutura cartilagínea hialina em processos de regeneração. Estudos que comparem propriedades da qualidade condrogênica das diferentes fontes permanecem escassos. Este estudo comparou a qualidade condrogênica das CTMs derivadas de líquido sinovial (CTMs-LS), medula óssea (CTMs-MO) e tecido adiposo (CTMs-AD) de equinos, por meio da avaliação da síntese de agrecam produzido por condrócitos diferenciados. Para tanto, 10 cavalos foram doadores de líquido sinovial (LS), medula óssea (MO) e de tecido adiposo (AD). As CTMs foram extraídas dessas três fontes, cultivadas e diferenciadas em condrócitos a partir de duas metodologias. No primeiro método utilizou-se cultura em pellets dentro de tubos cônicos, resultando em esferoides. O segundo método foi feito a partir da magnetização das células, com a formação de cultura tridimensional, originando microesferoides. A diferenciação condrogênica foi induzida com meio comercial (StemPro chondrogenesis differentiation kit Thermo Fisher Scientific) em ambos os métodos. Após o tempo de indução condrogênica, os esferoides e microesferoides foram incubados com hidrocloreto de guanidina (GuHCl) para extração de proteoglicanos. A concentração de agrecam foi quantificada por ELISA com anticorpo primário anti-agrecam monoclonal de cavalo para os esferoides e microesferoides. Como fator de correção as proteínas solúveis foram quantificadas pelo método BCA. Immunobloting foi realizado para identificar agrecam e queratam sulfato nos esferoides. Já a identificação do agrecam e queratam sulfato nos microesferoides foi demonstrada com o emprego de imunofluorescência por meio de microscopia de alta resolução confocal. As células em cultura, oriundas das diferentes fontes, demonstraram capacidade de aderência ao plástico e aparência fibroblastoide, confirmando característica e morfologia de CTMs. Ambas as metodologias proporcionaram diferenciação condrogênica. As concentrações das proteínas solúveis e agrecam foram maiores nos esferoides oriundos das CTMs-MO em comparação aos de CTMs-AD (P < 0.05) e as CTMs-LS não denotaram diferença estatística entre as duas fontes (P > 0.05). (Proteínas solúveis: CTM-MO 4.99±0.86; CTM-LS 4.14±1.03; CTM-AD 2.17±0.52) (Agrecam: CTM-MO 78.13±16.3; CTM-LS 63.8±25.11; CTM-AD 26.63±9.85). No entanto, as concentrações das razões agrecam/proteínas solúveis não apresentaram diferença estatística entre fontes (P > 0.05). (Agrecam/proteína solúvel: CTM-MO 25.14±11.62; CTM-LS 11.3±2.9; CTM-AD 14.2±6.81). O peso úmido dos esferoides foi maior nas CTMs-MO em comparação aos de CTMs-AD (P < 0.05) e as CTMs-LS não denotaram diferença estatística entre as duas fontes, contudo, a razão entre proteína solúvel por peso úmido e agrecam por peso úmido não demonstraram diferença significativa (P > 0.05). (Peso úmido do esferoide: CTM-MO 9.79±2.4; CTM-LS 8.57±2.7; CTM-AD 5.17±3.5; Razão proteína solúvel/peso úmido: CTM-MO 63.84±29.74; CTM-LS 32.66±4.07; CTM-AD 50.82±7.61; Razão agrecam/peso úmido: CTM-MO 1.01±0.47; CTM-LS 0.32±0.07; CTM-AD 0.78±0.43). Agrecam e queratam sulfato foram identificados nos esferoides oriundos das três fontes, demonstrados pela técnica de Immunobloting. Nos microesferoides, as concentrações de proteínas solúveis foram maiores naqueles derivados de CTMs-AD em comparação às de CTMs-LS e CTMs-MO (P < 0.05). (Proteína solúvel: CTM-MO 27.7±2.57; CTM-LS 22.02±1.84; CTM-AD 35.22±2.82). Já as concentrações de agrecam foram superiores nos microesferoides derivados de CTMs-LS em relação às CTMs-MO e não diferiram estatisticamente das CTMs-AD (Agrecam CTM-MO 63.06±12.07; CTM-LS 141.21±25.49; CTM-AD 117.14±14.32). A razão do agrecam por proteínas solúveis diferiu estatisticamente, demonstrando superioridade das CTM-LS e CTMs-AD ao comparar com as CTMs-MO (Razão agrecam/proteínas solúveis CTM-MO 4.11±1.51; CTM-LS 8.15±1.62; CTM-AD 4.23±0.7). Os microesferoides de todas as fontes expressaram agrecam e queratam sulfato por imunofluorescência confocal. Conclui-se que as CTMs derivadas das três fontes produzem agrecam. Os esferoides de CTMs-AD produzem menor rendimento, mas desempenham eficiência igual às de CTMs-LS e CTMs-MO, confirmados pelas razões de agrecam por proteínas solúveis. Já em ambiente tridimensional, as CTMs-LS e CTMs-AD demonstram superioridade condrogênica. Por fim, as três fontes podem ser utilizadas em tratamentos intra-articulares, já em conjunto com biomateriais ou scaffolds deve-se recomendar a utilização de CTMs-LS ou CMTs-AD.

Mesenchymal stem cells (MSCs) represent a promising therapy for treatment of joint disorders in horses. They are qualified for this purpose because of the immunomodulation characteristics and possible regenerative effect. However, it has not yet been established which source of MSCs is the most indicated to create hyaline cartilage structure in regeneration processes. Studies that compare properties of chondrogenic quality from different sources remain scarce. This study compared the chondrogenic quality of the MSCs derived from synovial fluid (MSCs-SF), bone marrow (MSCs-BM) and adipose tissue (MSCs-AT) of horses, through the evaluation of the aggrecan synthesis by differentiated chondrocytes. For this purpose, 10 horses were donors of synovial fluid (SF), bone marrow (BM) and adipose tissue (AT). The MSCs were extracted from these three sources, cultured and differentiated into chondrocytes from two methodologies. In the first method, pellets were cultured inside conical tubes, resulting in spheroids. The second method was made from the magnetization of the cells, with the formation of three-dimensional culture, originating microspheres. Chondrogenic differentiation was commercially induced (StemPro chondrogenesis differentiation kit - Thermo Fisher Scientific) in both methods. After the chondrogenic induction time, the spheroids and microspheres were incubated with guanidine hydrochloride (GuHCl) to extract proteoglycans. Aggrecan concentration in the spheroids and microspheres was quantified by ELISA with primary monoclonal anti-aggrecan antibody. The soluble proteins were quantified by the BCA method as a correction factor. Immunobloting was performed to identify aggrecan and keratan sulfate on spheroids. The identification of the aggrecan and keratan sulfate in the microspheres was demonstrated by high resolution confocal microscopy immunofluorescence. Cells in culture from different sources showed ability to adhere to plastic and a fibroblastic appearance, confirming the characteristic and morphology of MSCs. Both methodologies provided chondrogenic differentiation. Concentrations of the soluble proteins and aggrecan were higher in the spheroids derived from the MSCs-BM compared to the MSCs-AT (P <0.05) and the MSCs-SF showed no statistical difference between the two sources (P> 0.05) (Soluble proteins: MSCs-SF 4.99±0.86; CTM-LS 4.14±1.03; CTM-AD 2.17±0.52) (Aggrecan: CTM-BM 78.13±16.3; MSCs-SF 63.8±25.11; MSC-AT 26.63±9.85). However, the concentrations of the aggrecan did not present statistical difference between sources (P> 0.05) (Agrecam / soluble protein: MSCs-BM 25.14 ± 11.62, MSCs-SF 11.3 ± 2.9, MSCs-AT 14.2±6.81). The wet weight of the spheroids was higher in the MSCs-BM than in the MSCs-AT (P <0.05) and the MSCs-SF showed no statistical difference between the two sources, however, the ratio between wet weight soluble protein and wet weight aggrecan showed no significant difference (P> 0.05) (Wet weight of the spheroids: MSCs-BM 9.79±2.4; MSCs-SF 8.57±2.7; MSCs-AT 5.17±3.5; Soluble protein / wet weight ratio: MSCs-BM 63.84±29.74; MSCs-SF 32.66±4.07; MSCs-AT 50.82±7.61; Aggrecan/ wet weight ratio: MSCs-BM 1.01±0.47; MSCs-SF 0.32±0.07; MSCs-AT 0.78±0.43). Aggrecan and keratan sulfate were identified in the spheroids from the three sources, demonstrated by the Immunobloting technique. In the microspheres, soluble proteins concentrations were higher in those derived from MSCs-AT compared to MSCs-SF and MSCs-BM (P <0.05) (Soluble proteins: MSCs-BM 27.7±2.57; MSCs-SF 22.02±1.84; MSCs-AT 35.22±2.82). However, the concentrations of aggrecan were higher in the microspheres derived from MSCs-SF in relation to the MSCs-BM and did not differ statistically from the MSCs-AT (Aggrecan: MSCs-BM 63.06±12.07; MSCs-SF 141.21±25.49; MSCs-AT 117.14±14.32). Soluble protein and aggrecan ratio differed statistically, demonstrating superiority of MSCs-SF and MSCs-AT when compared to the MSCs-BM (Aggrecan/ soluble proteins ratio: MSCs-BM 4.11±1.51; MSCs-SF 8.15±1.62; MSCs-AT 4.23±0.7). Microspheres from all sources expressed aggrecan and keratan sulfate by confocal immunofluorescence. It is concluded that the MSCs derived from the three sources produce aggrecan. The spheroids of MSCs-AT had lower productivity, but perform efficiency equal to those of MSCs-SF and MSCs-BM, that being confirmed by the aggrecan and soluble proteins ratio. The MSCs-SF and the MSCs-AT demonstrate chondrogenic superiority in three-dimensional environment. Finally, all three sources can be used in intra-articular treatments. In conjunction with biomaterials or scaffolds, the use of MSCs-SF or MSCs-AT should be recommended.

ANÁLISE IMUNOENZIMÁTICA SÉRICA DE CÃES ATÓPICOS SUBMETIDOS AO TRANSPLANTE DE CÉLULAS-TRONCO MESENQUIMAIS AVALIAÇÃO DO PERFIL INFLAMATÓRIO

A dermatite atópica canina (DAC) apresenta uma complexa relação entre a inflamação e a barreira cutânea. O envolvimento de resposta imunológica do tipo Th2 e Th1, bem como produção de citocinas pró inflamatórias têm sido relacionadas com o padrão inflamatório, sinais clínicos e a gravidade da doença. As células-tronco mesenquimais (CTM) possuem características imunomoduladoras, sendo altamente sugeridas para reduzir a produção de citocinas inflamatórias e melhorar a qualidade de vida de animais atópicos. Visando comparar o efeito das CTM em cães atópicos, realizamos um estudo randomizado, simples-cego, com período inicial de placebo em seis cães. Foram comparados os perfis séricos inflamatórios por ELISA, além de resposta clínica por CADESI-04 e escala analítica de prurido. Ao final do estudo, os cães melhoraram significantemente o padrão clínico por CADESI-04 (p < 0,001) e pela escala de prurido (p < 0,05), contudo não houve mudança no perfil inflamatório das citocinas. Foi observado reações adversas em dois animais do estudo. Concluindo, o uso de CTM pode ser eficaz na melhora da sintomatologia relacionada a doença.

Canine atopic dermatitis (CAD) presents a complex relationship between inflammation and cutaneous barrier. The involvement of Th2 and Th1 type immune responses, as well as the production of proinflammatory cytokines have been related to inflammatory pattern, clinical signs and severity of disease. Mesenchymal stem cells (MTCs) have immunomodulatory characteristics and are highly suggested to reduce the production of inflammatory cytokines and to improve quality of life of atopic animals. In order to compare effects of MTCs on atopic dogs, we performed a randomized, simple-blind, placebo-controlled study in 6 dogs. Inflammatory serum profiles were compared by ELISA, in addition to clinical response by CADESI-04 and analytical pruritus scale. At the end of the experiment, dogs significantly improved the clinical standard for CADESI-04 (p <0.001) and pruritus scale (p <0.05), however, there was no change in the inflammatory cytokine profile. Adverse reactions were observed in two study animals. Concluding that the use of CTM may be effective in improving symptoms related to disease.

Reparo de hérnia abdominal com pericárdio bovino associado a células-tronco mesenquimais em ratos Wistar / Abdominal Hernia Repair with Bovine Pericardium Seeded with Mesenchymal Stem Cells in Wistar Rats

Background: Biological membranes demonstrate superiority over synthetic ones for its biocompatibility and strength in the reduction of abdominal hernias. Recents tissue engineering researches add mesenchymal stem cells to biological membranes with the purpose of obtaining additional cellular proliferation and consequent muscle regeneration, using biological membranes as cellular scaffolds. This article aimed to study the influence of mesenchymal stem cells in muscle regeneration in abdominal hernias, reduced with biological membranes. Materials, Methods & Results: Adult Wistar rats underwent abdominal hernia-inducing. They were divided into two groups as to the form of treatment for the reduction of hernia: stem cells associated with biological membranes or only biological membranes. After the treatment the macro and microscopic reviews were carried out in days seven, 14 and 60 postoperatively. Preparation of bovine pericardium with glycerin 98% presented efficiency in decellularization and conservation, maintaining its strength and avoiding bacterial growth. The mesenchymal stem cells obtained from bone marrow of adult Wistar rats, had capacity of proliferation. The majority of the cells was positive for the expression of surface antigens CD44, CD29 and CD99 and was negative for CD 34. In the differentiation trials, the same cells were able to differentiate into adipocytes and osteocytes. With 24 h from co-cultivating adhesion of mesenchymal stem cells in the membranes was observed. There was no foreign body reaction or contamination of surgical wounds and there was intense postoperative neovascularization on seven days. All animals presented omentum adherence, but no adherence to other organs.There was no statistically difference for the different times in macroscopic assessment: deposition of fibrous tissue, implant integration. The same occurred with the microscopic evaluations between the different treatment groups. The groups of immediate and later repair presented different responses to treatment. Discussion: The use of rats as animal model was satisfactory, being suitable for surgical procedures and assessments of the abdominal cavity. The different results obtained between groups of immediate repair and late repair corroborate with the idea that there is difference between induction and repair models in the same surgery or in different surgeries with the time interval between the two, suggesting the need for methodologies that simulate the hernias chronicity. The cells used were classified as mesenchymal stem cells, because it met all the criteria of Mesenchymal and Tissue Stem Cell Committee of the International Society of Celullar Therapy. The membranes conserved with glycerin 98% demonstrated biocompatibility, because there was no rejection or necrosis, infection or exacerbated infl ammation. However the muscle regeneration was not obtained over the membranes - and the methodological difference in other latest experiments about the membranes decellularization and the co-cultivating - can leads to conclusion that the cells attached to membranes were insufficient in number to obtain the desired result. These results suggest the need of new research studies or co-cultivating times and decellularization methods of bovine pericardium for association with mesenchymal stem cells.

Abdominal hernia repair with bovine pericardium seeded with mesenchymal stem cells in Wistar rats / Reparo de hérnia abdominal com pericárdio bovino associado a células-tronco mesenquimais em ratos Wistar

Background: Biological membranes demonstrate superiority over synthetic ones for its biocompatibility and strength in the reduction of abdominal hernias. Recents tissue engineering researches add mesenchymal stem cells to biological membranes with the purpose of obtaining additional cellular proliferation and consequent muscle regeneration, using biological membranes as cellular scaffolds. This article aimed to study the influence of mesenchymal stem cells in muscle regeneration in abdominal hernias, reduced with biological membranes. Materials, Methods & Results: Adult Wistar rats underwent abdominal hernia-inducing. They were divided into two groups as to the form of treatment for the reduction of hernia: stem cells associated with biological membranes or only biological membranes. After the treatment the macro and microscopic reviews were carried out in days seven, 14 and 60 postoperatively. Preparation of bovine pericardium with glycerin 98% presented efficiency in decellularization and conservation, maintaining its strength and avoiding bacterial growth. The mesenchymal stem cells obtained from bone marrow of adult Wistar rats, had capacity of proliferation. The majority of the cells was positive for the expression of surface antigens CD44, CD29 and CD99 and was negative for CD 34. In the differentiation trials, the same cells were able to differentiate into adipocytes

Vários tipos de implantes, naturais ou sintéticos, vêm sendo testados no reparo cirúrgico de hérnias. As membranas biológicas, ou arcabouços dérmicos descelularizados, apresentam reduzida formação de aderência entre o implante e as vísceras, diminuição da formação de fístulas, infecções e recorrências. Também apresentam resistência suficiente para suportar a pressão abdominal, evitando deiscências e eviscerações. [...]

O IMPACTO DAS VIAS INTRAPANCREÁTICA, INTRAVENOSAE E INTRACAPSULAR RENAL NO TRANSPLANTE DE CÉLULAS-TRONCO MESENQUIMAIS - REGENERAÇÃO MORFOFUNCIONAL DO DIABETES TIPO 1 EXPERIMENTAL

O diabetes mellitus (DM) é uma das doenças que mais tem aumentado sua incidência na última década. As células-tronco mesenquimais derivadas de tecido adiposo (CTMs-TA) possuem características imunomoduladoras e reparadoras, sendo capazes de reverter efeitos sistêmicos da doença. Sendo assim, nosso trabalho teve como objetivo avaliar o impacto do transplante de CTMs-TA pelas vias intravenosa, intrapancreática e intra-capsular renal em ratos diabéticos e comparar a que melhor exerce efeito regenerador. Para o estudo, utilizamos 45 ratos, wistar, fêmeas, divididos em 5 grupos: GCS controle sadio; GCD controle diabético; GIV diabético, via intravenosa; GIP diabético, via intrapancreática; GIR diabético, via cápsula renal. Para a indução, utilizamos uma única aplicação intraperitoneal (i.p) de Aloxana (120mg/kg), e após 3 dias, os animais foram submetidos ao transplante com as CTMs-TA (2x106cel/animal). Após 15 dias do transplante, os animais foram eutanasiados. O transplante de CTMs-TA pela cápsula renal foi capaz de reverter a hiperglicemia, além de restaurar o diâmetro das ilhotas e restabelecer a função das massa -pancreática. Concluímos que a cápsula renal foi a que apresentou melhores resultados na regeneração morfofuncional do pâncreas diabético. As CTMs-TA utilizadas neste estudo foram capazes de exercer um importante efeito parácrino, podendo ser utilizadas como alternativa para a melhoria da qualidade de vida de indivíduos diabéticos.

Diabetes mellitus is one of the diseases that has increased your incidence in the last decade. Adipose-Derived Mesenchymal Stem Cells (ATMSCs) have immunomodulatory and regenerate characteristics, thus are capable of reverse the damages of the disease. Therefore, our study aimed to evaluate the impact of ATMSCs transplantation by the intravenous, intrapancreatic and intra-capsular renal routes in diabetic rats and detect the best route to promote regenerative effects. We used 45 female wistar rats, divided into 5 groups: GCS healthy control; GCD - diabetic control; GIV - diabetic, intravenous; GIP - diabetic, intrapancreatic route; GIR - diabetic, via renal capsule. For induction, we used a single intraperitoneal application (i.p) of Alloxan (120mg / kg) and after 3 days, the animals were transplanted with the ATMSCs (2x106/ animal). After 15 days of transplantation, the animals were euthanized. The transplantation of ATMSCs by the renal capsule were able to reverse hyperglycemia, besides restoring the islet diameter and restoring the function of -pancreatic mass. We conclude that the renal capsule presented the best results in the morphofunctional regeneration of the diabetic pancreas. The stem cells used in this study were able to exert an