Cellular modifications and biomaterial design to improve mesenchymal stem cell transplantation

Wong, Johnny Kuan Un; Mehta, Ashish; Vu, Tai Anh; Yeo, Giselle C.

doi:10.1039/d3bm00376k

Cited by 7 publications

(3 citation statements)

References 241 publications

(321 reference statements)

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“…Mesenchymal stem cells are multipotent stem cells and can be obtained from various organs including bone marrow, synovium, periosteum, adipose tissue, and skeletal muscle [136]. MSCs are attractive cell sources in regenerative medicine based on their abilities to self-renew and differentiate into mesenchymal tissue lineage [137]. During the last few years, the use of MSCs and their cell-free derivatives has seen an increasing number of applications in disparate medical fields, including chronic musculoskeletal conditions [138][139][140][141][142].…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

Homan,

Onodera,

Matsuoka

et al. 2024

Preprint

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Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

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Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

Homan,

Onodera,

Matsuoka

et al. 2024

Preprint

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“…This approach not only improves the ability of cells to reach and integrate into the target tissue but also ensures better overall outcomes for cell-based therapies. 14 Since the pioneering work by Bertozzi et al, who introduced exogenous oligosaccharides into the glycocalyx of cell membranes, the emergence of metabolic oligosaccharide engineering strategies has provided additional avenues for "cell membrane surface modification". 15,16 Metabolic oligosaccharide engineering involves the conversion of nonnatural oligosaccharides into activated nucleotide sugars through cellular biosynthetic pathways, followed by the delivery of these monosaccharides bearing unique chemical functional groups to cell surface glycan structures via intracellular metabolic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…For example, cell surface modification has been shown to significantly enhance the homing capability of human mesenchymal stem cells by increasing their recognition of homing and implantation signals. This approach not only improves the ability of cells to reach and integrate into the target tissue but also ensures better overall outcomes for cell-based therapies …”

Section: Introductionmentioning

confidence: 99%

Integrating Metabolic Oligosaccharide Engineering and SPAAC Click Chemistry for Constructing Fibrinolytic Cell Surfaces

Liu,

Yang,

Heng

et al. 2024

ACS Appl. Mater. Interfaces

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To effectively solve the problem of significant loss of transplanted cells caused by thrombosis during cell transplantation, this study simulates the human fibrinolytic system and combines metabolic oligosaccharide engineering with strainpromoted azide−alkyne cycloaddition (SPAAC) click chemistry to construct a cell surface with fibrinolytic activity. First, a copolymer (POL) of oligoethylene glycol methacrylate (OEGMA) and 6-amino-2-(2-methylamido)hexanoic acid (Lys) was synthesized by reversible addition−fragmentation chain transfer (RAFT) copolymerization, and the dibenzocyclooctyne (DBCO) functional group was introduced into the side chain of the copolymer through an active ester reaction, resulting in a functionalized copolymer DBCO-PEG4-POL with ε-lysine ligands. Then, azide functional groups were introduced onto the surface of HeLa model cells through metabolic oligosaccharide engineering, and DBCO-PEG4-POL was further specifically modified onto the surface of HeLa cells via the SPAAC "click" reaction. In vitro investigations revealed that compared with unmodified HeLa cells, modified cells not only resist the adsorption of nonspecific proteins such as fibrinogen and human serum albumin but also selectively bind to plasminogen in plasma while maintaining good cell viability and proliferative activity. More importantly, upon the activation of adsorbed plasminogen into plasmin, the modified cells exhibited remarkable fibrinolytic activity and were capable of promptly dissolving the primary thrombus formed on their surfaces. This research not only provides a novel approach for constructing transplantable cells with fibrinolytic activity but also offers a new perspective for effectively addressing the significant loss of transplanted cells caused by thrombosis.

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Superoxide dismutase 2 scavenges ROS to promote osteogenic differentiation of human periodontal ligament stem cells by regulating Smad3 in alveolar bone‐defective rats

Qiu,

Sun,

et al. 2023

Journal of Periodontology

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BackgroundOsteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is an essential event in alveolar bone regeneration. Oxidative stress may be the main inhibiting factor of hPDLSC osteogenesis. Superoxide dismutase 2 (SOD2) is a key antioxidant enzyme, but its effect on hPDLSC osteogenic differentiation is unclear.MethodsSeveral surface markers were detected by flow cytometry, and the differentiation potential of hPDLSCs was validated by alkaline phosphatase (ALP), Alizarin Red S, and Oil Red O staining. Osteogenic indicators of hPDLSCs were detected by real‐time quantitative polymerase chain reaction (RT‐qPCR), Western blotting, and ALP staining. Furthermore, alveolar bone defect rat models were analyzed through micro‐CT, hematoxylin and eosin, and Masson staining. The intracellular reactive oxygen species (ROS) level was evaluated by a ROS assay kit. Finally, the expression of SOD2, Smad3, and p‐Smad3 in hPDLSCs was detected by RT‐qPCR and Western blotting (WB).ResultsSOD2 positively regulated the gene and protein expressions of ALP, BMP6, and RUNX2 in hPDLSCs (p < 0.05). Ideal bone formation and continuous cortical bone were obtained by transplanting LV‐SOD2 hPDLSCs (lentivirus vector for overexpressing SOD2 in hPDLSCs) in vivo. Exogenous H2O2 downregulated osteogenic indicators (ALP, BMP6, RUNX2) in hPDLSCs (p < 0.05); this was reversed by overexpression of SOD2. WB results showed that the Smad3 and p‐Smad3 signaling pathways participated in the osteogenic process of SOD2 in hPDLSCs.ConclusionSOD2 positively regulated hPDLSC osteogenic differentiation in vitro and in vivo. Mechanistically, SOD2 promotes hPDLSC osteogenic differentiation by regulating the phosphorylation of Smad3 to scavenge ROS. This work provides a theoretical basis for the treatment of alveolar bone regeneration.

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Cellular modifications and biomaterial design to improve mesenchymal stem cell transplantation

Abstract: Research has advanced considerably since the first clinical trial of human mesenchymal stem cells (MSCs) in the early 1990s. During this period, our understanding of MSC biology and our ability...

Cited by 7 publications

References 241 publications

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

Integrating Metabolic Oligosaccharide Engineering and SPAAC Click Chemistry for Constructing Fibrinolytic Cell Surfaces

Superoxide dismutase 2 scavenges ROS to promote osteogenic differentiation of human periodontal ligament stem cells by regulating Smad3 in alveolar bone‐defective rats

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