Biomedical subjects

Mark L Wang

Publications and source records attributed to Mark L Wang.

6 recordsLinked to original sources

PubMed2004

Particle bioreactivity and wear-mediated osteolysis.

This review focuses on wear debris-mediated osteolysis, a major factor compromising the long-term success of total joint arthroplasty. Studies on retrieved implants and animal models, as well as in vitro studies on particle bioreactivity, suggest that wear-mediated periprosthetic osteolysis is unlikely to be caused solely by 1 particular cell type or particulate species, but is rather the cumulative consequence of a number of biological reactions. Our recent findings suggest 3 novel mechanisms of particle bioreactivity that may contribute to osteolysis: 1) exacerbated inflammation caused by elevated reactive oxygen species production by activated macrophages and osteoclasts, (2) impaired periprosthetic bone formation secondary to disrupted osteogenesis, and (3) compromised bone regeneration resulting from increased cytotoxic response of mesenchymal osteoprogenitor cells. Understanding the pathogenesis of wear-mediated osteolysis is needed to improve orthopedic implant biocompatibility and wear reduction, and to develop effective pharmacotherapies.

Animals↗

PubMed2003

Direct and indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles.

The most frequent complication of total joint arthroplasty is periprosthetic osteolysis initiated by an inflammatory response to orthopaedic wear debris, which if left untreated, can result in implant instability and failure, eventually requiring revision surgery. We have previously reported that osteogenic differentiation of human marrow stroma-derived mesenchymal stem cells (hMSCs) is suppressed upon exposure to titanium particles, accompanied by reduced bone sialoprotein (BSP) gene expression, diminished production of collagen type I and BSP, decreased cellular viability and proliferation, and inhibition of extracellular matrix mineralization. In this study, we have further investigated hMSC cytotoxicity upon exposure to submicron particles of commercially pure titanium (cpTi) and zirconium oxide (ZrO(2)). Our results showed that direct exposure to cpTi and ZrO(2) particles compromises cell viability through the induction of apoptosis, eliciting increased levels of the tumor suppressor proteins p53 and p73, in a manner dependent on material composition, particle dosage, and time. Additionally, conditioned medium collected from hMSCs exposed to cpTi particles, but not to ZrO(2) particles, is cytotoxic to hMSCs, inducing apoptosis in the absence of particles. These findings demonstrate that exposure to orthopaedically derived wear particles can compromise hMSC viability through the direct and indirect induction of apoptosis. Thus, prolonged in vivo exposure of marrow-derived hMSCs to implant-derived wear debris is likely to reduce the population of viable osteoprogenitor cells, and may contribute to poor periprosthetic bone quality and implant loosening.

Apoptosis↗

PubMed2003

A simple, high-yield method for obtaining multipotential mesenchymal progenitor cells from trabecular bone.

In vitro cultures of primary, human trabecular bone-derived cells represent a useful system for investigation of the biology of osteoblasts. Our recent discovery of the multilineage mesenchymal differentiation potential of trabecular bone-derived cells suggests the potential application of these cells as mesenchymal progenitors for tissue repair and regeneration. Such applications are crucially dependent on efficient cell-isolation protocols to yield cells that optimally proliferate and differentiate. In this study, we describe a simple, high-yield procedure, requiring minimal culture expansion, for the isolation of mesenchymal progenitor cells from human trabecular bone. Moreover, these cells retain their ability to differentiate along multiple mesenchymal lineages through successive subculturing. Cell populations isolated and cultured as described here allow the efficient acquisition of a clinically significant number of cells, which may be used as the cell source for tissue-engineering applications.

Aged↗

PubMed2003

Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone.

The in vitro culture of human trabecular bone-derived cells has served as a useful system for the investigation of the biology of osteoblasts. The recent discovery in our laboratory of the multilineage mesenchymal differentiation potential of cells derived from collagenase-treated human trabecular bone fragments has prompted further interest in view of the potential application of mesenchymal progenitor cells (MPCs) in the repair and regeneration of tissue damaged by disease or trauma. Similar to human MPCs derived from bone marrow, a clearer understanding of the variability associated with obtaining these bone-derived cells is required in order to optimize the design and execution of applicable studies. In this study, we have identified the presence of a CD73(+), STRO-1(+), CD105(+), CD34(-), CD45(-), CD144(-) cell population resident within collagenase-treated, culture-processed bone fragments, which upon migration established a homogeneous population of MPCs. Additionally, we have introduced a system of culturing these MPCs that best supports and maintains their optimal differentiation potential during long-term culture expansion. When cultured as described, the trabecular bone-derived cells display stem cell-like capabilities, characterized by a stable undifferentiated phenotype as well as the ability to proliferate extensively while retaining the potential to differentiate along the osteoblastic, adipocytic, and chondrocytic lineages, even when maintained in long-term in vitro culture.

Adipocytes↗

PubMed2002

Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells.

Long-term stability of arthroplasty prosthesis depends on the integration between osseous tissue and the implant biomaterial. Integrity of the osseous tissue requires the contribution of mesenchymal stem cells and their continuous differentiation into an osteoblastic phenotype. This study aims to investigate the hypothesis that exposure to wear debris particles derived from orthopaedic biomaterials affects the osteoblastic differentiation of human mesenchymal stem cells (hMSC). Upon in vitro culture in the presence of osteogenic supplements (OS), we observe that cultures of hMSCs isolated from femoral head bone marrow are capable of osteogenic differentiation, expressing alkaline phosphatase, osteocalcin, and bone sialoprotein (BSP), in addition to producing collagen type I and BSP accompanied by extracellular matrix mineralization. Exposure of OS-treated hMSCs to submicron commercially pure titanium (cpTi) particles suppresses BSP gene expression, reduces collagen type I and BSP production, decreases cellular proliferation and viability, and inhibits matrix mineralization. In comparison, exposure to zirconium oxide (ZrO2) particles of similar size did not alter osteoblastic gene expression and resulted in only a moderate decrease in cellular proliferation and mineralization. Confocal imaging of cpTi-treated hMSC cultures revealed patchy groups of cells displaying disorganized cytoskeletal architecture and low levels of extracellular BSP. These in vitro findings suggest that chronic exposure of marrow cells to titanium wear debris in vivo may contribute to decreased bone formation at the bone/implant interface by reducing the population of viable hMSCs and compromising their differentiation into functional osteoblasts. Understanding the nature of hMSC bioreactivity to orthopaedic wear debris should provide additional insights into mechanisms underlying aseptic loosening.

Alkaline Phosphatase↗

PubMed2002

Exposure to particles stimulates superoxide production by human THP-1 macrophages and avian HD-11EM osteoclasts activated by tumor necrosis factor-alpha and PMA.

Wear of orthopaedic implants generates particles capable of inducing bone resorption and aseptic loosening of the implant. The present study shows the combined effect of particles and cell activation on macrophage (THP-1) and osteoclast (HD-11EM) release of reactive oxygen and nitrogen species, providing insight into mechanisms that can lead to osteolysis. In the absence of cell activation, exposure of either cell type to submicron zirconia or latex particles did not elicit an increase in reactive oxygen and nitrogen species production. Suboptimal stimulation with 4 beta-phorbol-12-myristate-13-acetate (PMA) plus particles resulted in a synergistic release of superoxide (O2-), however, and a low-level production of nitric oxide small middle dot by THP-1 macrophages. Similarly, particle stimulation of tumor necrosis factor-alpha-activated THP-1 cells increased O2- release. Our findings show the synergistic effect of cell activation and wear particles on O2- production by activated macrophages and osteoclasts, suggesting O2- involvement in mediating osteolysis.

Animals↗