Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (

The peptidergic innervation of human dental pulp was studied with indirect immunofluorescence and immunoperoxidase techniques. Pulpal nerve fibres displaying immunoreactivity for cholecystokinin, calcitonin gene-related peptide, C-terminal flanking peptide of neuropeptide tyrosine, leucine-enkephalin, methionine-enkephalin, neuropeptide K, neuropeptide tyrosine, peptide with N-terminal histidine and C-terminal isoleucine, somatostatin-28, substance P and vasoactive intestinal polypeptide were observed. Immunoreactive axon varicosities were detectable within radicular and coronal nerve trunks and within the nerve plexus of Raschkow in the para-odontoblastic region. Many peptidergic nerve fibres were observed in association with blood vessels of various sizes. Substance P- and calcitonin-gene-related peptide-immunoreactive axons were visible in the odontoblastic layer. The occurrence of VIP- and PHI-immunoreactive fibres lends support to the hypothesis that human tooth may be supplied by parasympathetic nerves. The immunocytochemical results here shown provide a morphological basis to previous experimental studies concerning the possible roles of neuropeptides in nociception mechanisms, control of the blood flow and modulation of the inflammatory response in dental tissues.

Proliferating cell nuclear antigen (PCNA), also referred to as cyclin, is an auxiliary protein to DNA-polymerase delta and a proposed marker of replicating cells. We have investigated the applicability and limitations of PC10 monoclonal antibody to PCNA in a cell kinetics study of developing human and rat tissues by immunocytochemical and flow cytometric techniques. Our data demonstrate that the epitope recognized by PC10 antibody is resistant to wax embedding, but sensitive to aldehyde fixation; conversely, alcoholic fixative solutions preserve the immunoreactivity to PC10. Tissue distribution, DNA content and bromodeoxyuridine uptake confirm that PC10-immunoreactive cells in alcohol-fixed tissues are cycling (G1-, S- and G2-phases traversing) cells. It is concluded that the PC10 antibody can be regarded as a powerful tool to study cell kinetics and differentiation in developing tissues, provided that the tissue processing is adequate.

Recent advances in culturing technology has permitted the production of organotypic models that may be referred to as human skin equivalents (HSE). We have studied histochemical, ultrastructural, and kinetic aspects of an HSE composed by an epidermal equivalent and a dermal equivalent separated by a basement membrane. Only keratinocytes and fibroblasts were present in the epidermal and dermal equivalents, respectively; cells of other lineages were lacking. Keratinocyte stratification and differentiation seemed similar to natural skin. Evidence is shown that such an HSE may also release growth factors such as vascular endothelial growth factor that are believed to play a role in skin grafting. The distribution of cycling cells as well as the values of the growth fraction are comparable to those observed in natural skin. Although the absence of several cells populations that reside in natural skin is a remarkable feature of this HSE, the high levels of tissue organization and cell differentiation lead us to believe that such an HSE may be considered a candidate substitute of human skin in biological, pharmacologic, and clinical applications. Anat Rec 264: [261][262][263][264][265][266][267][268][269][270][271][272] 2001.

Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the occurrence and distribution in human nasal mucosa of endothelin, a potent vasoconstrictor peptide, by immunocytochemistry and the effect of systemic administration of endothelin-1 on vascular perfusion of rabbit nasal mucosa by laser Doppler flowmetry. Endothelin-like immunoreactivity was demonstrated within vascular endothelial cells in both developing and mature human mucosa. Nasal epithelial cells and some connective tissue cells, presumed to be macrophages, also displayed specific immunostaining. In rabbits injected with endothelin-1, a potent and prolonged nasal vasoconstriction was observed. It is suggested that endothelin released locally may participate in the regulation of nasal blood flow via paracrine mechanisms. Since endothelin has growth-promoting actions on several cell types, it is also tentatively proposed that this regulatory peptide may play a role during development of the nose.