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Biomedical subjects

Thomas Engstrand

Publications and source records attributed to Thomas Engstrand.

4 recordsLinked to original sources

Three-dimensional technology and bone morphogenetic protein in frontal bone reconstruction.

Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to facilitate healing of bony defects. The effect of different BMPs is, as with many other growth factors, highly dependent on the delivery vehicle. Bovine type I collagen is currently used in the clinical setting as a carrier and has been approved in several countries for human use. Here, we report the reconstruction of a frontal bone defect using heparin together with bovine type I collagen, hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created on the back of the patient by treating the latissimus dorsi muscle with the growth factor. A polyamide mold was used as a template to achieve the desired shape. The bone structure was transplanted into the defect site via microsurgical techniques. Although the prefabricated bone was not large enough tocover the entire frontal defect, the reconstruction was completed by using an additional cranial implant.

Animals↗

Regeneration of human auditory nerve. In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion.

Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage.

Adult↗

Molecular biologic aspects of cartilage and bone: potential clinical applications.

The formation of cartilage and bone tissue from condensing mesenchymal stem cells is taking place in the early stage embryo, but also in the growth plate and during fracture repair in adults. Resident mesenchymal stem cells have been identified in bone marrow, periosteum, and in muscles. These pluripotent cells are attractive as therapeutic cells in cartilage and bone reconstructive procedures, since they can differentiate into chondrocytes and osteoblasts upon appropriate stimuli, such as certain growth factors. Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta1-3, bone morphogenetic proteins (BMPs), and activins, are essential mediators in cell proliferation and differentiation and play regulatory roles in cartilage and bone formation. This review presents functional data on TGF-beta1 in cartilage formation, BMP2 and BMP3 in bone formation, and a role of the BMP-regulatory protein noggin in BMP2 processing. Potential clinical applications of these proteins are further demonstrated and discussed.

Animals↗

Keratinocytes inhibit expression of connective tissue growth factor in fibroblasts in vitro by an interleukin-1alpha-dependent mechanism.

The wound healing process concludes with downregulation of fibroblast activity. Clinical observations suggest that the regenerating epidermis suppresses this activity. An important regulator of fibroblast activity is the fibrogenic cytokine connective tissue growth factor. We hypothesized that epidermal keratinocytes may affect fibroblast activity via this cytokine. We demonstrate keratinocyte-mediated suppression of connective tissue growth factor at both the mRNA and protein levels by around 50% or more when fibroblasts were cultured in multiwell plates with keratinocyte cultures in accompanying semipermeable cell culture inserts, or stimulated by keratinocyte-conditioned media. Both basal and transforming-growth-factor-beta1-stimulated levels of connective tissue growth factor were inhibited. A 3 h coculture period with keratinocytes was sufficient to suppress connective tissue growth factor expression by fibroblasts, but the inhibition developed over a time period of around 16 h. The putative keratinocyte-derived factor(s) responsible for these effects was found to be soluble and stable. By analyzing cytokines secreted by keratinocytes we identified interleukin-1alpha as a potent inhibitor of connective tissue growth factor mRNA expression in fibroblasts. Involvement of this cytokine in keratinocyte-mediated connective tissue growth factor suppression was confirmed by using anti-interleukin-1alpha antibodies. Tumor necrosis factor alpha or prostaglandins did not appear to be involved. In conclusion, our results indicate that interleukin-1alpha secretion by keratinocytes provides a mechanism for the downregulation of connective tissue activity during the end-stage of wound healing, when epithelia coverage has developed over the wound area.

Coculture Techniques↗