Type II Collagen-Conjugated Mesenchymal Stem Cells Micromass for Articular Tissue Targeting

Abstract

The tissue engineering approach in osteoarthritic cell therapy often requires the delivery of a substantially high cell number due to the low engraftment efficiency as a result of low affinity binding of implanted cells to the targeted tissue. A modification towards the cell membrane that provides specific epitope for antibody binding to a target tissue may be a plausible solution to increase engraftment. In this study, we intercalated palmitated protein G (PPG) with mesenchymal stem cells (MSCs) and antibody, and evaluated their effects on the properties of MSCs either in monolayer state or in a 3D culture state (gelatin microsphere, GM). Bone marrow MSCs were intercalated with PPG (PPG-MSCs), followed by coating with type II collagen antibody (PPG-MSC-Ab). The effect of PPG and antibody conjugation on the MSC proliferation and multilineage differentiation capabilities both in monolayer and GM cultures was evaluated. PPG did not affect MSC proliferation and differentiation either in monolayer or 3D culture. The PPG-MSCs were successfully conjugated with the type II collagen antibody. Both PPG-MSCs with and without antibody conjugation did not alter MSC proliferation, stemness, and the collagen, aggrecan, and sGAG expression profiles. Assessment of the osteochondral defect explant revealed that the PPG-MSC-Ab micromass was able to attach within 48 h onto the osteochondral surface. Antibody-conjugated MSCs in GM culture is a potential method for targeted delivery of MSCs in future therapy of cartilage defects and osteoarthritis.

The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles

“…In a classic study, since hMSCs do not express E-selectin ligands, researchers used an enzyme preparation (a-1,3-fucosyltransferase preparation) to convert MSCs expressing CD44 into hematopoietic cell E- selectin/L-selectin ligand, thus giving MSCs the ability to bind E-selectin and ultimately allowing MSCs to migrate to the targets [ 70 ]. Conjugation of antibodies to MSCs is currently a popular strategy, for example, Sulaiman et al used palmitated protein G (PPG) as a mediator and MSCs were successfully coupled to type II collagen antibody, increasing the ability to bind to the osteochondral surface [ 71 ]. Liao et al increased the hepatic accumulation capacity and therapeutic efficacy of ADSCs by conjugating the targeting peptide RLTRKRGLK on the surface of ADSCs by a bioorthogonal click chemistry [ 72 ].…”

Modification of mesenchymal stem cells for cartilage-targeted therapy

“…In the lipidation method, palmitate-conjugated protein A/G is bound to the Fc region of the Ab [58]. Palmitatederivatized antibodies against vascular adhesion molecules ICAM-1, VCAM-1 and MAdCAM-1 have been shown to enhance the homing of surface-engineered cells [64][65][66]. Dennis et al embedded lipidated protein G into the membranes of chondrogenic progenitor cells, allowing subsequent binding of anchor protein G antibodies to cartilage matrix antigens on the extracellular surface.…”

“…Cells coated with multiple antibodies were found to preferentially adhere to cartilage repair sites when added to rabbit cartilage explants [ 67 ]. Modifying the cell membrane with palmitate-conjugated type II collagen enables efficient targeted delivery of therapeutic MSCs to the osteochondral defect explant [ 64 ]. These results suggest that coating cell membranes with antibodies against matrix molecules effectively promotes the adhesion of MSCs to specific cartilage damage locations.…”