Treatment of human ulcers by application of macrophages prepared from a blood unit

Danon, D.; Madjar, Jack; Edinov, Elia; Knyszynski, Ahuva; Brill, Shai; Diamantshtein, Leah; Shinar, Eilat

doi:10.1016/s0531-5565(97)00094-6

Cited by 54 publications

(61 citation statements)

References 11 publications

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“…Third, human anti-Gal Abs immunocomplexed with α-gal epitopes readily bind to FcγR on macrophages (21, 32). Fourth, cultured human macrophages activated in vitro by hypotonic shock were found to accelerate wound healing in patients with deep sternal wounds (53) and with ulcers (7). The use of α-gal liposomes on wound dressings is likely to be much easier to perform than injection of activated macrophages into wounds because it does not require specialized equipment and facilities for in vitro culturing of macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages are further activated within the wound to secrete a variety of cytokines that recruit additional cells and induce their proliferation, thereby promoting regeneration of the injured tissue. Injection of activated macrophages into wounds of patients was reported to promote wound healing (7). These data led to the hypothesis that induction of rapid in situ recruitment of macrophages into wounds and localized activation of these cells may accelerate healing.…”

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confidence: 99%

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Rapid Recruitment and Activation of Macrophages by Anti-Gal/α-Gal Liposome Interaction Accelerates Wound Healing

Wigglesworth

Racki

Mishra

et al. 2011

The Journal of Immunology

179

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Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Gala1-3Galb1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ~1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95–100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Rapid Recruitment and Activation of Macrophages by Anti-Gal/α-Gal Liposome Interaction Accelerates Wound Healing

Wigglesworth

Racki

Mishra

et al. 2011

The Journal of Immunology

179

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“…11,12,14 In brief, a wholeblood unit donated routinely by healthy young donors (age range between 18 to 30 years) was collected into a triple blood-bag system. The unit was then separated into packed red cells, white blood cells (buffy coat), and plasma.…”

Section: Preparation Of Amsmentioning

confidence: 99%

“…19 In addition, in elderly and sick patients with impaired resident macrophage function, injection of allogeneic AMS promotes wound healing and confirms the therapeutic effect of donor AMS. 11,12 Finally, the beneficial effect of allogeneic cells can be explained by the modulation of local immune reactions in response to apoptosis of the transplanted cells. 7 It has been suggested that apoptotic cell ingestion by macrophages induces expression of anti-inflammatory cytokines that could suppress the damage of excessive inflammatory response.…”

Section: Limitationsmentioning

confidence: 99%

“…9,10 In the past few years we have treated Ͼ1500 elderly and sick patients with unhealed ulcers and wounds by local injections of human activated macrophage suspension (AMS). [11][12][13] Based on our favorable clinical experience, we hypothesized that the unique wound healing properties of macrophages could be exploited to promote healing and repair of the infarcted myocardium. Thus, the aim of conducting the present study was to test this hypothesis in a rat model of extensive MI.…”

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confidence: 99%

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Ex Vivo Activated Human Macrophages Improve Healing, Remodeling, and Function of the Infarcted Heart

et al. 2006

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Background-Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. Methods and Results-Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (Ϸ4ϫ10 5 cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (nϭ8) immediately after coronary artery ligation. The control group (nϭ9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells.

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Macrophage plasticity: signaling pathways, tissue repair, and regeneration

Yan,

Wang,

Cai

et al. 2024

MedComm

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Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll‐like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.

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Treatment of human ulcers by application of macrophages prepared from a blood unit

Cited by 54 publications

References 11 publications

Rapid Recruitment and Activation of Macrophages by Anti-Gal/α-Gal Liposome Interaction Accelerates Wound Healing

Rapid Recruitment and Activation of Macrophages by Anti-Gal/α-Gal Liposome Interaction Accelerates Wound Healing

Ex Vivo Activated Human Macrophages Improve Healing, Remodeling, and Function of the Infarcted Heart

Macrophage plasticity: signaling pathways, tissue repair, and regeneration

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