Surface Engineering for Cell-Based Therapies: Techniques for Manipulating Mammalian Cell Surfaces

Abstract

The introduction of cell-based therapies has provided new and unique strategies to treat many diseases and disorders including the recent approval of CAR-T cell therapy for the leukemia. Cell surface engineering is a methodology in which the cell surface is tailored to modulate cellular function and interactions. In addition to genetic engineering of cell surface proteins, a wide array of robust, innovative and elegant approaches have been developed to selectively target the cell surface. In this review, we will introduce the leading strategies currently used in cell surface engineering including broadly reactive chemical ligations and physical associations as well as more controlled approaches as demonstrated in genetic, enzymatic and metabolic engineering. Prominent applications of these strategies for cell-based therapies will be highlighted including targeted cell death, control over stem cell fate, immunoevasion, blood transfusion and the delivery of cells to target tissues. Advances will be focused specifically on cells which are the most promising in generating cell-based therapeutics including red blood cells, white blood cells (lymphocytes, macrophages), stem cells (multipotent and pluripotent), islet cells, cancer cells, and endothelial cells.

Harnessing Biology to Deliver Therapeutic and Imaging Entities via Cell‐Based Methods

“…Modified Sites AdvantagesD isadvantages cellular hitchhiking non-specificm ilda ttachmentconditionsw eak adherence cellular backpacks local patchesonc ell surface morestable adherence complexity of deposition methods biotin-avidin variable strong linkage, modular large protein conjugation native amino acids thiols, primary amines single step modification internalizationb yc ells, synthetic cargo modification click chemistry incorporated azido-sugars chemically orthogonal long incubation times, multi-step within hours at room temperature. [91] Thiss urface functionalization has found varied applications from cell targeting [92] to loading drugs or therapeutic particles. [93] Streptavidin-like proteins conjugated to biotinylated NPs on NSCs and MSCs have been shownt of acilitatet umor-selective distribution in intracranial [94] and tumor tropic [93] drug delivery, respectively.I nb oth cases, cell viability was not affected, and NSC-NP conjugates studied in the glioma model had improved distribution and retention versusN Ps alone.…”

Nanotechnology in cell replacement therapies for type 1 diabetes

“…PEG and its derivatives are among the most widely applied biomaterials in tissue engineering [324][325][326]. PEG has many desirable properties for cell encapsulation, such as versatile and relatively mild gelation conditions [327], ECM mimicry [328], the ability to conceal surface antigens [329], and the ability to be functionalized with a wide variety of biological agents [324,330]. It is also a suitable host-interfacing material because of its high hydrophilicity, which endows the polymer with low-fouling and low-opsonization characteristics [331,332].…”

Advances on Non-Genetic Cell Membrane Engineering for Biomedical Applications

“…When modifying substances conjugated with an appropriate hydrophobic anchor are admixed with cultured cells, the hydrophobic moiety can spontaneously insert into the hydrophobic zone between the lipid bilayer, thus anchoring the conjugated cargoes on the cell surface [31].…”

“…Non-genetic cell surface engineering can be broadly divided into covalent chemical conjugation and noncovalent physical bioconjugation. Those different non-genetic cell surface engineering strategies are summarized in many recent reviews [10,19,25,26,[31][32][33][34][35]. Among these, the non-genetic cell surface engineering that is used to modulate and investigate cell functions and control cell-cell and cell-microenvironment interactions can be found in previous review articles [29,32,34].…”

“…Among these, the non-genetic cell surface engineering that is used to modulate and investigate cell functions and control cell-cell and cell-microenvironment interactions can be found in previous review articles [29,32,34]. The application of non-genetic cell surface engineering to improve the therapeutic potential of whole-cell-based therapeutics has been reviewed previously [10,19,26,31]. The non-genetic engineering of extracellular vesicles has been discussed in recent reviews [21,22].…”