Rose Asrican | PubMed Health

PubMed2002

The specificity of phenotypic induction of mouse and human stem cells by signaling complexes.

Controlling the specific differentiation of stem cells (SCs) is a goal sought by many because of the benefits it would yield for repair or replacement of damaged tissues and organs. We report the discovery of signaling complexes and describe their use in predictably guiding the differentiation of mouse and human SCs. The signaling complexes (Signal-plexes [S-ps]) induce mouse and human SCs to express specific phenotypes. The S-ps have been used to identify a new source of human SCs (Hu abba-1) and have been shown to induce differentiation of multiple tissue-specific phenotypes selectively in mouse pluripotent embryonic cells as well as in Hu abba-1 cells. Endocrine and exocrine pancreas, liver, lung, kidney, heart, cartilage, bone, and other cell types have been induced in SCs by S-ps, as shown by morphology, immunostaining, enzyme-linked immunosorbent assay, and reverse transcriptase-polymerase chain reaction analysis.

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Tissue-engineered hybrid tooth and bone.

Tooth loss accompanied by alveolar bone resorption presents a significant clinical problem. We have investigated the utility of a tissue-engineering approach to provide corrective therapies for tooth-bone loss. Hybrid tooth-bone tissues were bioengineered as follows. Tooth implants were generated from pig third molar tooth bud cells seeded onto polyglycolide (PGA) and polyglycolide-colactide (PLGA) scaffolds, and grown for 4 weeks in the omenta of adult rat hosts. Bone implants were generated from osteoblasts induced from bone marrow progenitor cells obtained from the same pig, seeded onto PLGA fused wafer scaffolds, and grown for 10 days in a rotational oxygen-permeable bioreactor system. The tooth and bone implants were harvested, sutured together, reimplanted, and grown in the omenta for an additional 8 weeks. Histological and immunohistochemical analyses of the excised hybrid tooth-bone constructs revealed the presence of tooth tissues, including primary and reparative dentin and enamel in the tooth portion of hybrid tooth-bone implants, and osteocalcin and bone sialoprotein-positive bone in the bone portion of hybrid tooth-bone constructs. Collagen type III-positive connective tissue resembling periodontal ligament and tooth root structures were present at the interface of bioengineered tooth and bone tissues. These results demonstrate the utility of a hybrid tooth-bone tissue-engineering approach for the eventual clinical treatment of tooth loss accompanied by alveolar bone resorption.

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