Cell surface engineering and application in cell delivery to heart diseases

Abstract

Cell-based therapy has expanded its influence in cancer immunotherapy, regenerative medicine, and tissue engineering. Due to their secretory functions, differentiation capabilities, specific homing effects through chemotaxis, distinctive therapeutic potentials, and ex vivo expandability, cells have become an attractive reagent for advanced therapeutic strategies. Therefore, the ability to modify cells and manipulate their functions according to intended therapeutic designs has been the central scientific interest in the field of biomedical research. Many innovative methods have been developed with genetic modification of cells being the most advanced cell surface engineering technique. Although genetic modification is a powerful tool, it has a limited applicability due to the permanent modifications made on cells. Alternatively, many endeavors have been made to develop surface engineering techniques that can circumvent the limitations of genetic modification. In this review, current methods of non-genetic cell surface modification, including chemical conjugations, polymeric encapsulation, hydrophobic insertion, enzymatic and metabolic addition, will be introduced. Moreover, cell surface engineering plausible for cardiac remodeling and the future prospective will be discussed at the end.

Keywords: Cell surface engineering; cardiac diseases; cardiac repair; cell modification; cell therapy; mesenchymal stem cells.

Fig. 1

Modes of non-genetic cell surface engineering techniques. (1) Incorporation of cross-linkers, such as NHS, Maleimide, or pyridyldithiol, allows cell surface modification with biomaterials through chemical covalent conjugation. Cell metabolism of unnatural sugar and enzymatic reactions can be exploited to attach functional groups on the cell surface. (2) Electrostatic interactions between the cell surface and the charged polymers such as PEI, PLL, PAA, and PSS can modify cells through layer-by-layer technique. Also, charged block-co-polymers, such as PLL-PEG, can modify the cell surface through electrostatic interaction. (3) Lipid-conjugated bioactive molecules or polymers with long alkyl chains can be embedded into the cell membrane through hydrophobic interaction. Abbreviations: NHS: N-hydroxyl-succinimidyl ester; ManNAz: N-α-azidoacetylmannosamine; PAA: Poly(acrylic acid); PEG: Poly(ethylene glycol); PEI: Poly(ethyleneimine); PLL: Poly-L-lysine; PSS: Poly(styrene) sulfate; PVA: Poly(vinyl alcohol); SiaNAz: N-α-azidoacetyl sialic acid

Fig. 2

Schematic representation of surface-engineered MSCs for cardiac regeneration. Ex vivo cultured and expanded MSCs were surface engineered through hydrophobic insertion to incorporate rCXCR4 on their membrane. Hydrophobic insertion generated homogeneous MSCs modified with hydrophobized rCXCR4 within a short time. Systemically infused rCXCR4-modified MSCs can migrate to the ischemic myocardium by taking advantage of SDF-1 concentration gradient. Abbreviations: MSCs: mesenchymal stem cells; PEG: Poly(ethylene glycol); rCXCR4: Recombinant CXC chemokine receptor 4; SDF-1: Stromal-derived factor-1