Synergistic Actions of Hematopoietic and Mesenchymal Stem/Progenitor Cells in Vascularizing Bioengineered Tissues

Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs) and mesenchymal stem/progenitor cells (MSCs) were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP) scaffolds, followed by infusion of gel-suspended CD34+ hematopoietic cells. Co-transplantation of CD34+ HSCs and CD34− MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromized mice yielded vascularized tissue. The average vascular number of co-transplanted CD34+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34+ cells. Based on additional in vitro results of endothelial differentiation of CD34+ cells by vascular endothelial growth factor (VEGF), we adsorbed VEGF with co-transplanted CD34+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone, adipose, muscle and dermal grafts, and may have implications in the regeneration of internal organs

How to Treat Cartilage Injuries in the Ankle Joint by BMDC' s Transplantation

Osteochondral lesions of the ankle joint are defects of the cartilaginous surface and underlying subchondral bone, typically affecting the talus, most frequently traumatic in origin. Osteochondral lesions are often asymptomatic and may be treated conservatively, taking care to follow the patient over time. Bigger lesions, or higher grade lesions, especially in adult patients, are usually painful and hardly respond to a conservative treatment. So(( that,)) surgical treatment is frequently indicated. Thanks to technical advancements, regenerative techniques are quickly moving from traditional periostium based autologous chondrocyte implantation (ACI) to bone marrow derived cell transplantation (BMDCT). The introduction of a biodegradable scaffold based on the benzylic ester of hyaluronic acid for cell support and proliferation represented a first advancement toward a full arthroscopic procedure and significatively decreased the morbidity of ACI procedure in the ankle joint. Still two surgeries were required. Recently, BMDCT has been proposed as a technique capable to provide a repair of the lesion by hyaline cartilage in a one step procedure. Mesenchymal stem cells have the ability to differentiate into osteoblasts and chondroblasts. The rationale of the \u201cone-step technique\u201d is to transplant the entire bone-marrow cellular pool instead of isolated and expanded mesenchymal stem cells. This allows cells to be processed directly in the operating room, without the need for a laboratory phase, and BMDCT to be performed in \u201cone step\u201d. With a dedicated kit a total amount of about 60 ml of bone marrow aspirate is harvested from the posterior iliac crest, with the patient in prone decubitus. A scaffold and the instrumentation previously used for ACI are then used for an entirely arthroscopic implantation. Autologous platelet-rich fibrin (PRF) is added in order to provide a supplement of growth factors. The results of this procedure have been confirmed by biopsies and T2 mapping MRI and are clinically encouraging at mid-term. Evolution in surgical technique, new biomaterials and more recently the use of BMDCs permitted a marked reduction in procedure morbidity and costs up to a \u201cone step\u201d technique able to overcome the drawbacks of previous repair techniques. The stability of the results needs to be followed long term

Efeito da atividade física no osso normal e na prevenção e tratamento da osteoporose Efectos de la actividad física en huesos normales y en la prevención y tratamiento de osteoporosis Effect of the physical activity on normal bone and on the osteoporosis prevention and treatment

A osteoporose é uma doença cada vez mais diagnosticada em mulheres e homens de todo o mundo. Embora os esteróides sexuais sejam importantes na gênese da osteoporose, a inatividade física constitui um fator de risco. O exercício físico atua no osso por efeito direto, via força mecânica, ou indireto, mediado por fatores hormonais. Mas os mecanismos pelos quais a atividade física melhora a massa óssea ainda não são totalmente conhecidos. Baseando-se nos resultados que demonstram os efeitos benéficos da atividade física no tecido ósseo, a prática de esportes vem sendo cada vez mais indicada na prevenção e até mesmo no tratamento da osteoporose. O objetivo desta revisão é descrever os efeitos da atividade física no tecido ósseo normal e na prevenção e tratamento da osteoporose.<br>La osteoporosis es una enfermedad que cada vez más se diagnostica en mujeres y hombres de todo el mundo. Aunque los esteroides sexuales sean importantes en la génesis de la osteoporosis, la inactividad física constituye un factor de riesgo. El ejercicio físico actúa en el hueso de forma directa, vía fuerza mecánica, o indirecta, mediado por factores hormonales. Sin embargo la patogénesis por la que la actividad física mejora la masa ósea todavía no es totalmente conocida. Con base en los resultados que demuestran los efectos benéficos de la actividad física en el tejido óseo, la práctica de deportes viene siendo indicada cada vez más como medio de prevención y hasta incluso como tratamiento de la osteoporosis. El objetivo de esta revisión es describir los efectos de la actividad física en el tejido óseo normal y en la prevención y tratamiento de la osteoporosis.<br>Osteoporosis has been increasingly diagnosed in women and men worldwide. Although the sexual steroids are important in the genesis of human osteoporosis, it is believed that the lack of physical activity constitutes a risk factor. Physical activity acts on the bone by direct effect via mechanical force, or indirect effect through hormonal factors. However, the mechanism through which physical activity improves the bone mass is not completely known. Sports practice has been increasingly recommended for prevention and even treatment of osteoporosis based on the results that have demonstrated the beneficial effects of physical activity on the bone tissue. The goal of this review is to describe the effects of physical activity in the normal bone tissue and on the osteoporosis prevention and treatment