CCL21-loaded 3D hydrogels for T cell expansion and differentiation

Río, Eduardo Pérez Del; Santos, Fabião; Rodrı́guez, Xavier; Martínez-Miguel, Marc; Roca-Pinilla, Ramon; Arı́s, Anna; García‐Fruitós, Elena; Veciana, Jaume; Spatz, Joachim P.; Ratera, Imma; Guasch, Judith

doi:10.1016/j.biomaterials.2020.120313

Cited by 48 publications

(44 citation statements)

References 82 publications

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“…* p < 0.05) Reproduced with permission. [ 59 ] Copyright 2020, Elsevier. (CCL21 is a cytokine known to regulate T‐cell migration and proliferation; hADSCs: human adipose‐derived stem cells; hDMECs: human dermal microvascular endothelial cells; HPMC: hydroxypropyl methylcellulose; LEPCs: lymphatic endothelial precursor cells; VEGF‐C: vascular endothelial growth factors).…”

Section: Hydrogels To Regenerate Lymphatic Systemmentioning

confidence: 99%

“…Del Río et al showed that synthetic hydrogels that mimic lymph nodes can be used to promote the proliferation of T cells for sustaining the therapeutic effects of cell‐based cancer immunotherapy like CAR‐T therapy. [ 59 ] The team synthesized hydrogels using biologically inert polyethylene glycol (PEG) with low molecular weight anticoagulant heparin covalently linked to it. PEG provided similar structural and mechanical support as native lymph node tissues while heparin was used to electrostatically immobilized the cytokine, CCL21, which is known to regulate T‐cell migration and proliferation, to the hydrogel scaffold.…”

Section: Hydrogels To Regenerate Lymphatic Systemmentioning

confidence: 99%

“…Gelatin [40] Fibrin [41,48] Alginate [45] Collagen [48] Peptide [51] HPMC [53] PEG [59] 3D structure, mechanical properties such as stiffness and aqueous resembling native tissues and ECM matrices Network structure for high drug loading capability ECM-like matrices and aqueous content for implanted cells viability Porous/biodegrade property for sustained drug release Continuous pore-channels allows intercellular junction as conducive to the formation of tissue Biocompatibility/biodegradability to prevent adverse immune reactions…”

Section: Regenerate Lymphatic Systemmentioning

confidence: 99%

“…Table 1 shows a list of hydrogel materials that has been used for engineering the immune system, This technique is typically used in freeze-dried samples, but it enables to image the structure of hydrated hydrogels if a special protocol at the vacuum chamber is utilized. [59] It is recommended to characterize the morphology of hydrated hydrogel instead of freeze-dried samples, as the internal porous structure and network may be collapsed and damaged during the lyophilization. c) Assays can also be used for characterizing the size of nanogel.…”

Section: Modulate Inflammationmentioning

confidence: 99%

“…Abbreviation: AFM ¼ Atomic force microscope; CCK-8 ¼ Cell counting kit-8; CD ¼ Circular dichroism; CLSM ¼ Confocal laser scanning microscope; CR ¼ Congo red; DCs ¼ dendritic cell; DLS ¼ Dynamic light scattering; DMA ¼ Dynamic mechanical analyzer; ELISA ¼ Enzyme-linked immunosorbent assay; FCM ¼ Flow cytometry; FT-IR ¼ Fouriertransform infrared spectroscopy; H and E staining¼ Hematoxylin and eosin staining; HPLC ¼ High-performance liquid chromatography; IVIS ¼ In vivo imaging system; MTT ¼ 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NF-κB/AP-1 ¼ Nuclear factor κB and activator protein 1; NMR ¼ Nuclear magnetic resonance; SEM ¼ Scanning electron microscope; TEM ¼ Transmission electron microscopy; UV-vis ¼ Ultraviolet-visible spectroscopy; VCA ¼ Viable count assay; XRD ¼ X-ray diffraction; XTT ¼ 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2 H-tetrazolium hydroxide. b)This technique is typically used in freeze-dried samples, but it enables to image the structure of hydrated hydrogels if a special protocol at the vacuum chamber is utilized [59]. It is recommended to characterize the morphology of hydrated hydrogel instead of freeze-dried samples, as the internal porous structure and network may be collapsed and damaged during the lyophilization.…”

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Hydrogels for Engineering the Immune System

Shou

Tay

2021

Advanced NanoBiomed Research

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Human immune system has evolved as one of the most powerful defense systems to protect against invading pathogens and mutated cells. However, when persistent immune suppression or activation occurs, it can lead to adverse, chronic physiological effects including cancer and arthritis. Hydrogels are soft materials that can be engineered to modulate immune responses through controlled biomolecule release/adsorption, regeneration of lymphoid tissues, and enhanced antigen presentations. This is achieved by programming hydrogels to exhibit optimal properties such as porosity, biodegradability, and biocompatibility to interface seamlessly with the immune system. Herein, recent innovations and future challenges are described using programmable hydrogels to regenerate the lymphatic system, modulate inflammation, and enhance cancer immunotherapy. Key properties of hydrogels are also highlighted for engineering the immune system and techniques to characterize these properties.

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Section: Hydrogels To Regenerate Lymphatic Systemmentioning

confidence: 99%

Section: Hydrogels To Regenerate Lymphatic Systemmentioning

confidence: 99%

Section: Regenerate Lymphatic Systemmentioning

confidence: 99%

Section: Modulate Inflammationmentioning

confidence: 99%

mentioning

confidence: 99%

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Hydrogels for Engineering the Immune System

Shou

Tay

2021

Advanced NanoBiomed Research

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Biohybrid Hydrogels for Tumoroid Culture

Castellote‐Borrell,

Merlina,

Rodríguez

et al. 2023

Advanced Biology

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Tumoroids are 3D in vitro models that recapitulate key features of in vivo tumors, such as their architecture — hypoxic center and oxygenated outer layer — in contrast with traditional 2D cell cultures. Moreover, they may be able to preserve the patient‐specific signature in terms of cell heterogeneity and mutations. Tumoroids are, therefore, interesting tools for improving the understanding of cancer biology, developing new drugs, and potentially designing personalized therapeutic plans. Currently, tumoroids are most often established using basement membrane extracts (BME), which provide a multitude of biological cues. However, BME are characterized by a lack of well‐defined composition, limited reproducibility, and potential immunogenicity as a consequence of their natural origin. Synthetic polymers can overcome these problems but lack structural and biochemical complexity, which can limit the functional capabilities of organoids. Biohybrid hydrogels consisting of both natural and synthetic components can combine their advantages and offer superior 3D culture systems. In this review, it is summarized efforts devoted to producing tumoroids using different types of biohybrid hydrogels, which are classified according to their crosslinking mechanism.

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Lymph‐Node‐Targeted Drug Delivery for Effective Immunomodulation to Prolong the Long‐Term Survival After Heart Transplantation

et al. 2022

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The chronic rejection responses and side effects of the systematic administration of immunosuppressants are the main obstacles to heart allograft and patient survival. The development of xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, it is demonstrated that lymph‐node (LN)‐targeted drug delivery can realize LN‐specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong long‐term survival after heart transplantation in a chronic murine heart transplantation model. A chemokine C‐C motif ligand 21 (CCL21) specific aptamer for LN targeting is decorated onto the surface of the hybrid nanoparticular delivery vector mainly composed of CaCO3/CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, fingolimod hydrochloride (FTY720), in draining lymph nodes (dLNs) for inducing powerful immune suppression. By promoting the generation of endogenous regulatory T cells (Tregs) and decreasing the proportion of effector T cells (Teffs) in dLNs after heart transplantation, the LN‐targeting strategy can effectively regulate local immune responses instead of systemic immunity, which reduces the incidence of long‐term complications. This study provides an efficient strategy to improve the survival rate after organ transplantation by precise and localized immunoregulation with minimized side effects of immunosuppression.

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CCL21-loaded 3D hydrogels for T cell expansion and differentiation

Cited by 48 publications

References 82 publications

Hydrogels for Engineering the Immune System

Hydrogels for Engineering the Immune System

Biohybrid Hydrogels for Tumoroid Culture

Lymph‐Node‐Targeted Drug Delivery for Effective Immunomodulation to Prolong the Long‐Term Survival After Heart Transplantation

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