Stem cell technology and bioceramics: From cell to gene engineering

Abstract

Mesenchymal stem cells reside in bone marrow and, when these cells are incorporated into porous ceramics, the composites exhibit osteo-chondrogenic phenotypic expression in ectopic (subcutaneous and intramuscular) or orthotopic sites. The expressional cascade is dependent upon the material properties of the delivery vehicle. Bioactive ceramics provide a suitable substrate for the attachment of the cells. This is followed by osteogenic differentiation directly on the surface of the ceramic, which results in bone bonding. Nonbioactive materials show neither surface-dependent cell differentiation nor bone bonding. The number of mesenchymal stem cells in fresh adult bone marrow is small, about one per one-hundred-thousand nucleated cells, and decreases with donor age. In vitro cell culture technology can be used to mitotically expand these cells without the loss of their developmental potency regardless of donor age. The implanted composite of porous ceramic and culture-expanded mesenchymal stem cells exhibits in vivo osteo-chondrogenic differentiation. In certain culture conditions, these stem cells differentiate into osteoblasts, which make bone matrix on the ceramic surface. Such in vitro prefabricated bone within the ceramic provides immediate new bone-forming capability after in vivo implantation. Prior to loading of the cultured, marrow-derived mesenchymal stem cells into the porous ceramics, exogenous genes can be introduced into these cells in culture. Combining in vitro manipulated mesenchymal stem cells with porous ceramics can be expected to effect sufficient new bone-forming capability, which can thereby provide tissue engineering approaches to patients with skeletal defects in order to regenerate skeletal tissues.

Recombinant growth/differentiation factor‐5 (GDF‐5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

“…[2][3][4] Kuboki et al 25 reported that the pore size of HA controlled phenotype expression in BMP-induced osteogenesis or chondrogenesis, and the commitment to osteogenic lineage occurred by increasing the pore size of porous HA ceramics. Although the mechanism that determines whether the MSCs differentiate into osteoblasts or chondroblasts is unclear, it appears that the differentiation of MSCs is strongly affected by the surrounding microenvironment such as oxygen tension, properties of biomaterials, cell densities, and so on.…”

“…1, 2 We already established an experimental model to show consistent bone formation in the pores of hydroxyapatite (HA) ceramic combined with the culture-expanded bone marrow mesenchymal stem cells (MSCs) from rat or human bone marrow. [2][3][4] The porous HA ceramic exhibits a biocompatible and osteoconductive nature and is therefore an excellent material for supporting the osteogenic differentiation of MSCs.…”

Fetal bone cells for tissue engineering

“…This has been recapitulated by different articles, particularly in the field concerning bone marrow-derived stem cells [3][4][5]. As one of every 100,000 nucleated cells derived from bone marrow is a stem cell, a procedure of isolation is required to decrease the volume of material injected [6].…”

Restoration of cellular function of mesenchymal stem cells from a hypophosphatasia patient

“…5 These cells have been identified in several tissues such as bone marrow, 6 adipose tissue, 7 synovial tissue 8 and dental papilla tissue. 9 MSCs are thought to be an effective tool for regenerative medicine.…”