Macrophage-based therapeutic strategies in regenerative medicine

Spiller, Kara L.; Koh, Timothy J.

doi:10.1016/j.addr.2017.05.010

Cited by 257 publications

(203 citation statements)

References 141 publications

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“…The plasticity of macrophages, that change according to the microenvironment and its different stimuli, make different subtypes a continuous rather than a strict classification, rendering the study of renal macrophage polarization in humans difficult . Possible macrophage‐based strategies to boost regeneration include injection of ex vivo activated macrophages, delivery of molecules that can alter macrophage numbers or phenotype, or design of biomaterials to alter macrophage phenotype, although none have yet been tested in clinical studies of AKI …”

Section: Cellular and Molecular Factors Associated With Renal Regenermentioning

confidence: 99%

Renal regeneration after acute kidney injury

et al. 2018

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Acute kidney injury is common and associated with negative renal and patient outcomes. The human kidney has a real but limited regeneration capacity. Understanding renal regeneration may allow us to manipulate this process and thus develop therapeutic weapons to improve patients' outcome. In the first part of this paper we discuss the clinical factors associated with renal recovery: baseline patient particularities, acute kidney injury characteristics and the medical approach taken in the short and long-term. In the second part, the cellular and molecular mechanisms underlying renal regeneration are explored. The immune system seems to have an important role, first promoting inflammation and then tissue healing. Other players, such as cellular senescence, mitochondrial dysfunction, renal haemodynamics and metabolic reprogramming also have a role in renal regeneration. We aim to develop a short review of renal regeneration, offering a holistic view of this process.

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Section: Cellular and Molecular Factors Associated With Renal Regenermentioning

confidence: 99%

Renal regeneration after acute kidney injury

et al. 2018

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“…Macrophages are also critical regulators of wound healing, capable of adapting to the microenvironment in order to regulate all phases of tissue repair, from inflammation to proliferation and remodeling . Macrophages are able to participate in these very different stages of wound healing by undergoing dramatic changes in phenotype, with the major phenotypes often denoted M1 (proinflammatory), M2a (associated with the resolution of wound healing), and M2c (associated with tissue remodeling) . M1 macrophages are associated with phagocytosis of microbes, and production of proinflammatory mediators .…”

Section: Introductionmentioning

confidence: 99%

Human macrophage response to microbial supernatants from diabetic foot ulcers

Deusenbery

Kalan

Meisel

et al. 2019

Wound Repair Regeneration

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Diabetic foot ulcers (DFUs) are a major clinical problem exacerbated by prolonged bacterial infection. Macrophages, the primary innate immune cells, are multifunctional cells that regulate diverse processes throughout multiple phases of wound healing. To better understand the influence of microbial species on macrophage behavior, we cultured primary human monocyte‐derived macrophages from four donors for 24 hours in media conditioned by bacteria and fungi (Pseudomonas aeruginosa, Corynebacterium amycolatum, Corynebacterium striatum, Staphylococcus aureus, Staphylococcus simulans, and Candida albicans) isolated from the DFUs of six patients. The effects of these microbe‐derived signals on macrophage behavior were assessed by measuring the gene expression of a panel of 25 genes related to macrophage phenotype, angiogenesis, bacterial recognition, and cell survival, as well as secretion of two inflammatory cytokines using NanoString multiplex analysis. Principal component analysis showed that macrophage gene expression and protein secretion were affected by both microbial species as well as human donor. S. simulans and C. albicans caused up‐regulation of genes associated with a proinflammatory (M1) phenotype, and P. aeruginosa caused an increase in the secretion of the proinflammatory cytokine and M1 marker tumor necrosis factor‐alpha (TNFα). Together, these results suggest that macrophages respond to secreted factors from microbes by up‐regulating inflammatory markers, and that the effects are strongly dependent on the monocyte donor. Ultimately, increased understanding of macrophage–microbe interactions will lead to the development of more targeted therapies for DFU healing.

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“…Prolonged inflammation is a characteristic of many diseases and disorders. Macrophages, the primary innate immune cells of the body, play a large role in directing inflammation within damaged tissues, but they can also promote tissue regeneration . Macrophages facilitate tissue regeneration by homing to injured tissue, phagocytosing necrotic and apoptotic debris, and secreting proteins that guide tissue regeneration .…”

Section: Introductionmentioning

confidence: 99%

Modulation of macrophage phenotype via phagocytosis of drug‐loaded microparticles

Wofford

Cullen

Spiller

2019

J Biomedical Materials Res

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Monocyte‐derived macrophages play a critical role in directing wound pathology following injury. Depending on their phenotype, macrophages also promote tissue regeneration. However, the therapeutic administration of macrophages with a controlled phenotype is challenging because macrophages are highly plastic and quickly revert to a detrimental, inflammatory phenotype in response to the environment of a damaged tissue. To address this issue, we developed a novel strategy to modulate macrophage phenotype intracellularly through phagocytosis of drug‐loaded microparticles. Poly(lactic‐co‐glycolic acid) microparticles loaded with the anti‐inflammatory drug dexamethasone (Dex) were phagocytosed by monocytes and stored intracellularly for at least 5 days. After differentiation into macrophages, cell phenotype was characterized over time with high‐throughput gene expression analysis via NanoString. We found that the microparticles modulated macrophage phenotype for up to 7 days after microparticle uptake, with decreases in inflammation‐related genes at early timepoints and upregulation of homing‐ and phagocytosis‐related genes at multiple timepoints in a manner similar to cells treated with continuous free Dex. These data suggest that intracellularly loading macrophages with Dex microparticles via phagocytosis could be a unique methodology to selectively modulate macrophage phenotype over time. This strategy would allow therapeutic administration of macrophages for the treatment of a number of inflammatory disease and disorders. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1213–1224, 2019.

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Macrophage-based therapeutic strategies in regenerative medicine

Cited by 257 publications

References 141 publications

Renal regeneration after acute kidney injury

Renal regeneration after acute kidney injury

Human macrophage response to microbial supernatants from diabetic foot ulcers

Modulation of macrophage phenotype via phagocytosis of drug‐loaded microparticles

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