Tumorigenesis by Millipore Filters in Mice: Histology and Ultrastructure of Tissue Reactions as Related to Pore Size2

Karp, Richard D.; Johnson, Kenneth H.; Buoen, L. C.; Ghobrial, Helmy K. G.; Brand, I; Brand, K. Gerhard

doi:10.1093/jnci/51.4.1275

Cited by 99 publications

(52 citation statements)

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“…The work was stimulated by almost 40 years of observation that the FBR to an implanted material is modulated by roughness, porosity, and/or texture [20][21][22][23]. Our porous scaffold materials, prepared by sphere templating, are characterized by a single pore size (in contrast to a pore size distribution), with pores spherical in shape and interconnected.…”

Section: The Future Of Biocompatibilitymentioning

confidence: 99%

The Biocompatibility Manifesto: Biocompatibility for the Twenty-first Century

Ratner

2011

J. of Cardiovasc. Trans. Res.

122

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Section: The Future Of Biocompatibilitymentioning

confidence: 99%

The Biocompatibility Manifesto: Biocompatibility for the Twenty-first Century

Ratner

2011

J. of Cardiovasc. Trans. Res.

122

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“…In contrast to PDMS, cellulose Millipore filters are porous. 20 In this study, we have used both types of biomaterials to test their FBR in mice. The phenotype of SPARC-null mice, which includes alterations in ECM assembly, led us to ask whether SPARC might be involved in one or more aspects of the FBR.…”

mentioning

confidence: 99%

Compromised Production of Extracellular Matrix in Mice Lacking Secreted Protein, Acidic and Rich in Cysteine (SPARC) Leads to a Reduced Foreign Body Reaction to Implanted Biomaterials

Puolakkainen

Bradshaw

Kyriakides

et al. 2003

The American Journal of Pathology

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SPARC (secreted protein, acidic and rich in cysteine), a matricellular glycoprotein, modulates the interaction of cells with the extracellular matrix (ECM).Recently, accelerated cutaneous wound closure and altered deposition of collagen were reported in SPARC-null mice. Herein we asked whether SPARC might influence the foreign body reaction to biomaterial implants. Polydimethylsiloxane (silicone rubber) disks and cellulose Millipore filters were implanted into wild-type and SPARC-null mice. In wild-type animals, significant levels of SPARC were observed in the cells and the ECM comprising the capsules around the implants. After 4 weeks, SPARC-null mice exhibited a significant decrease in the thickness of the foreign body capsule, as compared to that observed in wildtype mice. A significant reduction in capsular vascular density was also associated with the silicone implants in the SPARC-null animals. Electron microscopy revealed that collagen fibers in the capsules produced by SPARC-null mice were smaller and more uniform in size than those in wild-type animals. Furthermore, staining with picrosirius-red showed that the collagen fibers were less mature in SPARC-null than in wild-type mice. The altered ECM resulting in decreased capsular thickness, indicative of an altered foreign body reaction in SPARC-null mice, implicates SPARC as an important modulator of the encapsulation of implanted biomaterials. (Am J Pathol 2003, 162:627-635) Extracellular matrix (ECM) can regulate the migration, proliferation, and/or differentiation of cells. The ECM is composed of structural proteins, proteoglycans, growth factors, and matricellular proteins that include thrombospondins 1 and 2, osteopontin, tenascin-C, and SPARC (secreted protein, acidic and rich in cysteine). Matricellular proteins are known to modulate cell-matrix interactions and aspects of the cell cycle that control proliferation or apoptosis.1,2 A number of matricellular proteins show increased expression in response to injury.2-4 For example, thrombospondin 2-null mice display accelerated excisional wound healing and an altered foreign body reaction (FBR) to silicone implants. 5,6 SPARC, also known as BM-40 and osteonectin, is a calcium-binding glycoprotein secreted by many cells, eg, fibroblasts, endothelial cells, and platelets.7-10 As a matricellular protein, SPARC does not contribute structurally to ECM; rather, it regulates the production of several ECM proteins.2 Two principal functions of SPARC are its modulation of cell shape and inhibition of cell-cycle progression.2 In vivo, SPARC is expressed in remodeling tissues, such as healing cutaneous wounds and bowel anastomoses, and during bone formation, adipogenesis, and angiogenesis.

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“…20 For example, tumors arise when filters with small holes are inserted subcutaneously in mice but not when filters composed of the same material, but with large holes, are similarly inserted. 21 Equally paradoxical is the observation that tumors arise in epithelial cells at a much higher rate than in controls when normal rat mammary epithelial cells are transplanted adjacent to stroma that had previously been exposed to a chemical carcinogen after clearing out the local epithelial cells. 22 It has been observed that just transplanting normal cells into another (untreated but inappropriate) stromal environment (eg, testis cells to kidney capsule) is enough to induce carcinoma predictably and that, despite the abnormal phenotype of the subsequent cancer cells, transplanting them back to their proper environment ensures that they return to normal.…”

Section: Introductionmentioning

confidence: 99%