RESUMO
OBJECTIVE: Tissue-engineered vascular grafts containing adipose-derived mesenchymal stem cells offer an alternative to small-diameter vascular grafts currently used in cardiac and lower-extremity revascularization procedures. Adipose-derived, mesenchymal stem cell-infused, tissue-engineered vascular grafts have been shown to promote remodeling and vascular homeostasis in vivo and offer a possible treatment solution for those with cardiovascular disease. Unfortunately, the time needed to cultivate adipose-derived mesenchymal stem cells remains a large hurdle for tissue-engineered vascular grafts as a treatment option. The purpose of this study was to determine if stromal vascular fraction (known to contain progenitor cells) seeded tissue-engineered vascular grafts would remain patent in vivo and remodel, allowing for a "same-day" process for tissue-engineered vascular graft fabrication and implantation. METHODS: Stromal vascular fraction, obtained from adult human adipose tissue, was seeded within 4 hours after acquisition from the patient onto poly(ester urethane)urea bilayered scaffolds using a customized rotational vacuum seeding device. Constructs were then surgically implanted as abdominal aortic interposition grafts in Lewis rats. RESULTS: Findings revealed patency in 5 of 7 implanted scaffolds at 8 weeks, along with neotissue formation and remodeling occurring in patent tissue-engineered vascular grafts. Patency was documented using angiography and gross inspection, and remodeling and vascular components were detected using immunofluorescent chemistry. CONCLUSIONS: A "same-day" cell-seeded, tissue-engineered vascular graft can remain patent after implantation in vivo, with neotissue formation and remodeling occurring by 8 weeks.
Assuntos
Tecido Adiposo/citologia , Aorta Abdominal/cirurgia , Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Transplante de Células-Tronco/instrumentação , Células Estromais/fisiologia , Células Estromais/transplante , Engenharia Tecidual/métodos , Alicerces Teciduais , Adulto , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Biomarcadores/metabolismo , Células Cultivadas , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Neointima , Fenótipo , Desenho de Prótese , Ratos Endogâmicos Lew , Células Estromais/metabolismo , Fatores de Tempo , Transplante Heterólogo , Grau de Desobstrução Vascular , Remodelação Vascular , Fluxo de TrabalhoRESUMO
Abstract Validation of transendocardial injection as a method for delivering therapeutic agents to the diseased heart is increasing. Puncture heart biopsies should re-emerge as a possible alternative method to allow access to the myocardium and implantable biomaterial for cell therapy. Therefore, this work aims to present a percutaneous puncture device for biopsy and intramyocardial biomaterial injection, standardize the technique and attest to the safety of the method. The adaptation consists of creating myocardial microlesions that allow for better fixation of stem cells. The objective of this technical note covers only the development of the needle and the histological quality of the biopsies. It has not been used in humans yet.
Assuntos
Humanos , Animais , Biópsia por Agulha/métodos , Transplante de Células-Tronco/métodos , Miocárdio , Agulhas , Biópsia por Agulha/instrumentação , Reprodutibilidade dos Testes , Transplante de Células-Tronco/instrumentaçãoRESUMO
Validation of transendocardial injection as a method for delivering therapeutic agents to the diseased heart is increasing. Puncture heart biopsies should re-emerge as a possible alternative method to allow access to the myocardium and implantable biomaterial for cell therapy. Therefore, this work aims to present a percutaneous puncture device for biopsy and intramyocardial biomaterial injection, standardize the technique and attest to the safety of the method. The adaptation consists of creating myocardial microlesions that allow for better fixation of stem cells. The objective of this technical note covers only the development of the needle and the histological quality of the biopsies. It has not been used in humans yet.
Assuntos
Biópsia por Agulha/métodos , Miocárdio , Agulhas , Transplante de Células-Tronco/métodos , Animais , Biópsia por Agulha/instrumentação , Humanos , Reprodutibilidade dos Testes , Transplante de Células-Tronco/instrumentaçãoRESUMO
The instrument has a locking mechanism and is composed of an external needle with blunt tip, with multiple 0.5 mm diameter holes. Internally it is fitted with a mandrill needle, which can be mobilized inside occluding or releasing the lateral holes. The procedure for producing micro lesions is done by exchanging the blunt mandrill for a brush-mandrill, provided with micro bristles that are structurally designed to fill the holes with small exteriorization of bristles. As an option to brush mandrill there is a second self-expandable feather shaped mandrill.
Assuntos
Miocárdio , Agulhas , Transplante de Células-Tronco/instrumentação , Desenho de Equipamento , Humanos , Punções/instrumentação , Reprodutibilidade dos Testes , Transplante de Células-Tronco/métodosRESUMO
El deterioro funcional de un órgano o tejido es un problema médico grave y de alto costo, ya que la sustitución de estas estructuras involucra, entre otros, múltiples factores de orden científico, económico y ético. La medicina busca en la actualidad convertir en realidad la regeneración de los tejidos mediante el desarrollo de terapias para restaurar, en el cuerpo humano, las células y los tejidos envejecidos o dañados. En esta comunicación preliminar presentamos una serie de pacientes donde se utilizaron células mesenquimales, mononucleares, autólogas, obtenidas de la médula ósea de la cresta ilíaca del propio enfermo, para tratar distintas afecciones. Desde noviembre de 2005 hasta mayo 2011, tratamos 23 pacientes, con un promedio de edad de 55,39 años. Once pseudoartrosis; 2 retardos de consolidación; 3 alargamientos óseos; 1 defecto osteo-tegumentario de tibia; 3 pacientes con necrosis óseas asépticas; 1 quiste óseo de cuello femoral; 4 artrosis incipientes de rodilla; 1 lesión del manguito rotador del hombro y 1 entesitis crónica aquiliana. El procedimiento se realizó en todos los casos en forma ambulatoria. Todos los procedimientos se realizaron en quirófano bajo anestesia general breve y con rigurosa asepsia. Utilizamos métodos reglados para cosechar células madre mesenquimáticas mononucleares de médula ósea del propio enfermo. Igualmente de manera reglada se cosecha sangre periférica del paciente para obtener, una vez procesada, plasma enriquecido con plaquetas y lisado de plaquetas. Logramos consolidación clínica y radiológica en 10 de los 11 casos de peudoartrosis (90,90 por ciento), en los 2 casos de retardo de consolidación, en los 3 alargamientos óseos y en el defecto osteo-tegumentario de tibia...
The functional impairment of an organ or tissue is a serious and high cost medical problem. The replacement of these structures involves multiple scientific, economical and ethical issues. All medical physicians and researchers are working nowadays to make possible tissue regeneration by developing therapies to restore damaged, aged or dead cells and tissues of the human body. At this preliminary report we present a series of patients, with various pathologies, in which we used autologous mononuclear mesenchymal cells, harvested from the bone marrow of the patient's iliac crest. Since November 2005 until May 2011, 23 patients, with an average age of 55,39 years, were treated: 11 non unions; 2 delayed unions; 3 bone lengthening; 1 tibia severe lesion of soft tissue and loss of bone; 3 aseptic osteo necrosis; 1 femoral neck bone cyst, 4 mild knee osteoarthritis, 1 rotator cuff injury and 1 chronic Achilles enthesitis. All were ambulatory patients. Performed in an operating room, with strict aseptic conditions, under short general anesthesia. The autologous bone marrow with mesenchymal mononuclear stem cells was harvested under predetermined protocols. Also, pre determined protocols were used to collect the patient's peripheral blood to be sent to the laboratory to obtain platelet rich plasma (PRP) and concentrated lyses platelets in plasma. We achieved clinical and radiological osseous union in: 10 of 11 non unions (90, 90 percent), in 2 delayed unions, in 3 bone lengthening and also in the tibia's severe soft tissue and bone defect. Based on this experience we can conclude that the stimulation of bone consolidation with a concentrated autologous mesenchymal stem cells, obtained from the patient's iliac crest, resulted to be a safe, reliable, minimally invasive procedure with a high rate of success...
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Medicina Regenerativa/tendências , Regeneração Nervosa , Transplante de Células-Tronco/instrumentação , Transplante de Células-Tronco/métodos , Engenharia Celular , Pseudoartrose/cirurgia , Pseudoartrose/terapia , Transplante HomólogoRESUMO
El deterioro funcional de un órgano o tejido es un problema médico grave y de alto costo, ya que la sustitución de estas estructuras involucra, entre otros, múltiples factores de orden científico, económico y ético. La medicina busca en la actualidad convertir en realidad la regeneración de los tejidos mediante el desarrollo de terapias para restaurar, en el cuerpo humano, las células y los tejidos envejecidos o dañados. En esta comunicación preliminar presentamos una serie de pacientes donde se utilizaron células mesenquimales, mononucleares, autólogas, obtenidas de la médula ósea de la cresta ilíaca del propio enfermo, para tratar distintas afecciones. Desde noviembre de 2005 hasta mayo 2011, tratamos 23 pacientes, con un promedio de edad de 55,39 años. Once pseudoartrosis; 2 retardos de consolidación; 3 alargamientos óseos; 1 defecto osteo-tegumentario de tibia; 3 pacientes con necrosis óseas asépticas; 1 quiste óseo de cuello femoral; 4 artrosis incipientes de rodilla; 1 lesión del manguito rotador del hombro y 1 entesitis crónica aquiliana. El procedimiento se realizó en todos los casos en forma ambulatoria. Todos los procedimientos se realizaron en quirófano bajo anestesia general breve y con rigurosa asepsia. Utilizamos métodos reglados para cosechar células madre mesenquimáticas mononucleares de médula ósea del propio enfermo. Igualmente de manera reglada se cosecha sangre periférica del paciente para obtener, una vez procesada, plasma enriquecido con plaquetas y lisado de plaquetas. Logramos consolidación clínica y radiológica en 10 de los 11 casos de peudoartrosis (90,90 por ciento), en los 2 casos de retardo de consolidación, en los 3 alargamientos óseos y en el defecto osteo-tegumentario de tibia...(AU)
The functional impairment of an organ or tissue is a serious and high cost medical problem. The replacement of these structures involves multiple scientific, economical and ethical issues. All medical physicians and researchers are working nowadays to make possible tissue regeneration by developing therapies to restore damaged, aged or dead cells and tissues of the human body. At this preliminary report we present a series of patients, with various pathologies, in which we used autologous mononuclear mesenchymal cells, harvested from the bone marrow of the patients iliac crest. Since November 2005 until May 2011, 23 patients, with an average age of 55,39 years, were treated: 11 non unions; 2 delayed unions; 3 bone lengthening; 1 tibia severe lesion of soft tissue and loss of bone; 3 aseptic osteo necrosis; 1 femoral neck bone cyst, 4 mild knee osteoarthritis, 1 rotator cuff injury and 1 chronic Achilles enthesitis. All were ambulatory patients. Performed in an operating room, with strict aseptic conditions, under short general anesthesia. The autologous bone marrow with mesenchymal mononuclear stem cells was harvested under predetermined protocols. Also, pre determined protocols were used to collect the patients peripheral blood to be sent to the laboratory to obtain platelet rich plasma (PRP) and concentrated lyses platelets in plasma. We achieved clinical and radiological osseous union in: 10 of 11 non unions (90, 90 percent), in 2 delayed unions, in 3 bone lengthening and also in the tibias severe soft tissue and bone defect. Based on this experience we can conclude that the stimulation of bone consolidation with a concentrated autologous mesenchymal stem cells, obtained from the patients iliac crest, resulted to be a safe, reliable, minimally invasive procedure with a high rate of success...(AU)