Biology subjects

Lanham, S.

Publications and source records attributed to Lanham, S..

4 recordsLinked to original sources

bioRxiv2025

DC-SIGN Binding to the Surface Ig Oligomannose-type Glycans Promotes Follicular Lymphoma Cell Adhesion and Survival

The occupation of the surface immunoglobulin antigen-binding site by oligomannose-type glycans (sIg-Mann) is a tumor-specific post-translational modification of classic follicular lymphoma (FL). SIg-Mann switches binding from antigen to dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), known to be expressed on interfollicular macrophages and FL-associated follicular dendritic cells (FDCs). The interaction with DC-SIGN induces reorganization of sIg-Mann in wider and less dense clusters than anti-Ig, consistent with inefficient DC-SIGN-induced endocytosis and a low-level intracellular signaling. However, ligand-specific cell clusters form between sIg-Mann-expressing lymphoma and DC-SIGN-expressing cells, raising a need to understand the functional consequences of the interaction of DC-SIGN with sIg-Mann on primary FL cells. This engagement induces adhesion of FL cells to VCAM-1 via B-cell receptor proximal kinases and actin regulators in a fashion similar to anti-Ig, but without initiating apoptosis in vitro. Instead, antibody blockade of sIg-Mann contact with DC-SIGN expressed on FDC-derived YK6/SIGN cells inhibits adhesion and survival of primary FL cells in vitro. These data highlight that the specific interaction with DC-SIGN induces FL cell adhesion to VCAM-1, likely allowing FL cell retention in the lymph node, and survival of the FL cells. Adhesion and survival are inhibited by an anti-DC-SIGN blocking antibody, indicating a new early therapeutic approach against FL retention and survival in adaptive tumor tissue niches. Key pointsO_LIDC-SIGN promotes FL cell adhesion to VCAM-1 via B-cell receptor proximal kinases and actin regulators C_LIO_LIDC-SIGN interaction with sIg-Mann sustains the survival of FL cells C_LI

cancer biology↗

bioRxiv2023

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair but can fail to provide a long-term clinical resolution, emphasising the need for a functional biomimetic tissue engineering alternative. An attractive sustainable opportunity for tissue regeneration would be the application of human bone waste tissue for the synthesis of a material ink for 3D bioprinting of skeletal tissue. The use of human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate micro-environment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. Extrusion-based deposition was mediated by the blending of human bone-ECM (B) with nanoclay (L, Laponite(R)) and alginate (A) polymer, to engineer a novel material ink (LAB). The inclusion of nanofiller and polymeric material increased the rheological, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularisation following implantation in an ex vivo chick chorioallantoic membrane (CAM) model. Addition of bone morphogenetic protein-2 (BMP-2) with HBMSCs further enhanced vascularisation together with mineralisation after only 7 days. The current study demonstrates the synergistic combination of nanoclay with biomimetic materials, (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalised skeletal tissue repair. Graphical AbstractEngineering nanoclay-based bone ECM novel bioink for bone regeneration. Human bone trabecular tissue was demineralised, decellularised and blended with nanoclay (Laponite(R)) and alginate after digestion. The resulting ink was investigated for printability following rheological and filament fusion investigation. The microstructural arrangement of the blends was examined together with viability and functionality of bioprinted HBMSCs. Finally, the ability of the novel blend to support drug release ex vivo in a CAM model was determined confirming the potential of the bone ECM ink to support bone formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/536074v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@b9dc13org.highwire.dtl.DTLVardef@1f6f0dorg.highwire.dtl.DTLVardef@1b3c098org.highwire.dtl.DTLVardef@295192_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles

There is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the stromal osteogenic, adipogenic and chondrogenic lineages. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues have proved challenging as no single specific marker has been identified limiting understanding of SSC fate, immunophenotype and the widespread clinical application of these cells. While a number of cell surface markers can enrich for SSCs, none of the proposed markers, alone, provide a platform to isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. The current study details the application of oligonucleotide-coated nanoparticles, spherical nucleic acids (SNAs), to rapidly isolate human cells using mRNAs signatures detected in SSCs in real time, to identify stem and progenitor skeletal populations using single cell RNA sequencing. Based on scRNA-seq of samples from 11 patients, this method was able to identify novel targets for SSC enrichment, which were assessed in a total of 80 patients. This methodology was able to isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with a capacity for tri-lineage differentiation in vitro. The current approach provides new targets and a platform to advance SSC isolation, enrichment with significant therapeutic impact therein.

cell biology↗

bioRxiv2019

Optimising DNA-Coated Gold Nanoparticles to Enrich Skeletal Stem Cells from Human Bone Marrow Samples

Human bone marrow (BM) derived stromal cells contain a population of skeletal stem cells (SSCs), with the capacity to differentiate along the osteogenic, adipogenic and chondrogenic lineages enabling their application to clinical therapies. However, current methods, to isolate and enrich SSCs from human tissues remain, at best, challenging in the absence of a specific SSC marker. Unfortunately, none of the current proposed markers, alone, can isolate a homogenous cell population with the ability to form bone, cartilage, and adipose tissue in humans. Here, we have designed DNA-gold nanoparticles able to identify and sort SSCs displaying specific mRNA signatures. The current approach demonstrates the significant enrichment attained in the isolation of SSCs, with potential therein to enhance our understanding of bone cell biology and translational applications. TABLE OF CONTENTS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/882563v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@48c5acorg.highwire.dtl.DTLVardef@1a9d096org.highwire.dtl.DTLVardef@1bd4da2org.highwire.dtl.DTLVardef@133dd1d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗