Multinucleated giant cells within the in vivo implantation bed of a collagen-based biomaterial determine its degradation pattern

This study investigated the osteoinductive potential of granules of stoichiometric hydroxyapatite (HA) and 0.5% zinc containing hydroxyapatite (ZnHA) in intramuscular (IM) site of rabbit’s abdomen. The biomaterials were both used in granular form, with 75% porosity and particle diameter between 450 and 500μm, sintered at 1100°C. Both materials performed adequately on a multiparametric in vitro cytocompatibility assay, indicating their suitability for in vivo testing. After approval by the Ethics Commission on Teaching and Research in Animals, fifteen rabbits were submitted to general anesthesia, incision and tissue dilatation, and a small site was created for HA (right incision) and ZnHA (left incision) intramuscular implantation. The animals were killed after 2, 4 and 12 weeks for biomaterials and surrounding tissues removal. Histological analysis after 2 weeks revealed the presence of granulation tissue surrounding biomaterials with multinucleated giant cells and no newly formed bone for both materials. After 4 weeks there was fibrous tissue involving the material and few inflammatory cells. Following 12 weeks it was observed the presence of connective tissue surrounding the biomaterial, cellularized enough for the two experimental groups, but it was not observed the presence of bone matrix associated with the biomaterials. We conclude that both biomaterials are cytocompatible and did not present the property of osseoinduction after 12 weeks of implantation.

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Porcine Dermis and Pericardium-Based, Non–Cross-Linked Materials Induce Multinucleated Giant Cells After Their In Vivo Implantation: A Physiological Reaction?

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-14-00155 ◽

2015 ◽

Vol 41 (6) ◽

pp. e267-e281 ◽

Cited By ~ 18

Author(s):

Mike Barbeck ◽

Jonas Lorenz ◽

Marzellus Grosse Holthaus ◽

Nina Raetscho ◽

Alica Kubesch ◽

...

Keyword(s):

Mononuclear Cells ◽

Giant Cells ◽

Cellular Tissue ◽

Tissue Reaction ◽

Material Surface ◽

Multinucleated Giant Cells ◽

Barrier Membrane ◽

Tissue Reactions ◽

Early Degradation

The present study analyzed the tissue reaction to 2 novel porcine-derived collagen materials: pericardium versus dermis. By means of the subcutaneous implantation model in mice, the tissue reactions were investigated at 5 time points: 3, 10, 15, 30, and 60 days after implantation. Histologic, histochemical, immunhistologic, and histomorphometric analysis methodologies were applied. The dermis-derived material underwent an early degradation while inducing mononuclear cells together with some multinucleated giant cells and mild vascularization. The pericardium-derived membrane induced 2 different cellular tissue reactions. The compact surface induced mononuclear cells and multinucleated giant cells, and underwent a complete degradation until day 30. The spongy surface of the membrane induced mainly mononuclear cells, and served as a stable barrier membrane for up to 60 days. No transmembranous vascularization was observed within the spongy material surface layer. The present data demonstrate the diversity of the cellular tissue reaction toward collagen-based materials from different tissues. Furthermore, it became obvious that the presence of multinucleated giant cells was associated with the material breakdown/degradation and vascularization. Further clinical data are necessary to assess extent to which the presence of multinucleated giant cells observed here will influence the materials stability, integration, and, correspondingly, tissue regeneration within human tissue.

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In vitro and in vivo assessment of CaP materials for bone regenerative therapy. The role of multinucleated giant cells/osteoclasts in bone regeneration

Journal of Biomedical Materials Research Part B Applied Biomaterials ◽

10.1002/jbm.b.34388 ◽

2019 ◽

Vol 108 (1) ◽

pp. 282-297 ◽

Cited By ~ 1

Author(s):

Ana Carolina Cestari Bighetti ◽

Tania Mary Cestari ◽

Paula Sanches Santos ◽

Ricardo Vinicius Nunes Arantes ◽

Suelen Paini ◽

...

Keyword(s):

Bone Regeneration ◽

Giant Cells ◽

Regenerative Therapy ◽

Multinucleated Giant Cells ◽

In Vivo Assessment

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In vivo Implantation of a Bovine-Derived Collagen Membrane Leads to Changes in the Physiological Cellular Pattern of Wound Healing by the Induction of Multinucleated Giant Cells: An Adverse Reaction?

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2018.00104 ◽

2018 ◽

Vol 6 ◽

Cited By ~ 16

Author(s):

Sarah Al-Maawi ◽

Chakorn Vorakulpipat ◽

Anna Orlowska ◽

Tomislav A. Zrnc ◽

Robert A. Sader ◽

...

Keyword(s):

Wound Healing ◽

Adverse Reaction ◽

Giant Cells ◽

Collagen Membrane ◽

Multinucleated Giant Cells ◽

Cellular Pattern

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Transition of podosomes into zipper-like structures in macrophage-derived multinucleated giant cells

Molecular Biology of the Cell ◽

10.1091/mbc.e19-12-0707 ◽

2020 ◽

Vol 31 (18) ◽

pp. 2002-2020

Author(s):

Arnat Balabiyev ◽

Nataly P. Podolnikova ◽

Aibek Mursalimov ◽

David Lowry ◽

Jason M. Newbern ◽

...

Keyword(s):

Plasma Membranes ◽

Giant Cells ◽

Multinucleated Giant Cells ◽

E Cadherin

Our study reveals previously unrecognized actin-based zipper-like structures (ZLSs) formed between macrophage-derived multinucleated giant cells undergoing fusion in vivo and in vitro. It is shown that podosomes are precursors of these structures. The transition of podosomes into ZLSs is induced by bridging plasma membranes by E-cadherin and nectin-2.

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Morphological assessment of the development of multinucleated giant cells in glioma by using mitosis-specific phosphorylated antibodies

Journal of Neurosurgery ◽

10.3171/jns.2003.98.4.0854 ◽

2003 ◽

Vol 98 (4) ◽

pp. 854-859 ◽

Cited By ~ 8

Author(s):

Kenkou Maeda ◽

Masaaki Mizuno ◽

Toshihiko Wakabayashi ◽

Syuntarou Takasu ◽

Tetsurou Nagasaka ◽

...

Keyword(s):

Laser Scanning ◽

Giant Cells ◽

Laser Scanning Confocal Microscopy ◽

Multinucleated Giant Cells ◽

Content Type ◽

Scanning Confocal Microscopy ◽

Drug Treatments ◽

Fine Print

Object. The nature and origin of multinucleated giant cells in glioma have not been made clear. To investigate the phosphorylation of intermediate filaments, the authors studied multinucleated giant cells in vitro and in vivo by using mitosis-specific phosphorylated antibodies. Methods. Cultured human glioma cells were immunostained with monoclonal antibodies (mAbs) 4A4, KT13, and TM71, which recognized the phosphorylation of vimentin at Ser55, glial fibrillary acidic protein at Ser13, and vimentin at Ser71, respectively. Subsequently, the nature of multinucleated giant cells was investigated using laser scanning confocal microscopy. In addition, paraffin-embedded tissue sections obtained in three patients with giant cell glioblastoma were also investigated. Multinucleated giant cells were immunoreacted with the mAb 4A4 and not with KT13 and TM71 in vitro and in vivo. In addition, the authors obtained these results in multinucleated giant cells under natural conditions, without drug treatments. Conclusions. Findings in this investigation indicated that multinucleated giant cells are those remaining in mitosis between metaphase and telophase, undergoing neither fusion nor degeneration.

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Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction

mBio ◽

10.1128/mbio.02457-19 ◽

2019 ◽

Vol 10 (6) ◽

Cited By ~ 4

Author(s):

Maorong Xie ◽

Héloïse Leroy ◽

Rémi Mascarau ◽

Marie Woottum ◽

Maeva Dupont ◽

...

Keyword(s):

Dendritic Cells ◽

Cell Fusion ◽

Myeloid Cells ◽

Cell Spreading ◽

Giant Cells ◽

Target Cells ◽

Multinucleated Giant Cells ◽

Virus Transfer ◽

Hiv 1

ABSTRACT Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.

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Nanostructured Bone Grafting Substitutes Versus Autologous Cancellous Bone – An Animal Experiment in Sheep

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.631.202 ◽

2014 ◽

Vol 631 ◽

pp. 202-206

Author(s):

Thomas Gerber ◽

Cornelia Ganz ◽

Werner Götz ◽

Kai Helms ◽

Christoph Harms ◽

...

Keyword(s):

Bone Substitute ◽

Animal Experiment ◽

Giant Cells ◽

Multinucleated Giant Cells ◽

Synthetic Bone ◽

Synthetic Bone Substitute ◽

Hematoxylin And Eosin ◽

The Right ◽

Resorptive Activity

In an In vivo study the full synthetic bone substitute NanoBone® S (NBS) was analyzed using a standardized bone defect (6 x 12 x 24mm) model in the ovine tibial metaphysis. The defect on the left side was filled with NBS granules and on the right side, autologous bone, harvested from the hip of the same animal, was inserted. After six, 12 and 26 weeks sheep were sacrificed and the tibiae analyzed. Quantitative histomorphological analysis after six weeks showed a resorption of biomaterial from over 60 to 24 percent. In contrast the bone formation after 6, and 12 weeks revealed an osteoneogenesis of 19%, and 34%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity.

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Bio-Absorption of Human Dentin-Derived Biomaterial in Sheep Critical-Size Iliac Defects

Materials ◽

10.3390/ma14010223 ◽

2021 ◽

Vol 14 (1) ◽

pp. 223

Author(s):

Md Arafat Kabir ◽

Masaru Murata ◽

Mamata Shakya ◽

Katsuhisa Yamada ◽

Toshiyuki Akazawa

Keyword(s):

Bone Regeneration ◽

Critical Size ◽

Morphological Changes ◽

Giant Cells ◽

Human Tooth ◽

Micro Ct ◽

Multinucleated Giant Cells ◽

Custom Made ◽

Histological Images

The aim of this study was to evaluate the bio-absorption and bone regeneration of human tooth-derived dentin scaffold, entitled as perforated root-demineralized dentin matrix (PR-DDM), after in vivo implantation into the critical-size iliac defects. The dentin scaffolds were prepared from human vital, non-functional teeth. Thirty artificial macro-pores (Ø 1 mm) were added after removing the enamel portion. The modified teeth were supersonically demineralized in 0.34 N HNO3 for 30 min. The microstructure was observed by scanning electron microscope (SEM). The 3D micro-CT and histological analysis were carried out to evaluate the bio-absorption of PR-DDM at 2 and 4 months. A smooth dentin collagen surface with symmetrical macro-pores and tube-type dentinal tubules (Ø 1–2 µm) with micro-cracks were observed on the perforated region. A significant number of custom-made macro-pores disappeared, and the size of the macro-pores became significantly wider at 4 months compared with the 2 months (p < 0.05) evaluated by 3D micro-CT. Histological images revealed the presence of multinucleated giant cells attached to the scalloped border of the PR-DDM. The morphological changes due to bio-absorption by the cellular phagocytes were comparable to the 3D micro-CT and histological images at 2 and 4 months. Altogether, the results demonstrated that the PR-DDM block was gradually absorbed by multinucleated giant cells and regenerated bone. Human PR-DDM might serve as a unique scaffold for extraoral bone regeneration.

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