Balancing macrophage polarization via stem cell-derived apoptotic bodies for diabetic wound healing

Mao, Jiayi; Qian, Shutong; Zhao, Qiuyu; Zhao, Binfan; Lu, Bolun; Zhang, Liucheng; Mao, Xiyuan; Zhang, Yuguang; Cui, Wenguo; Sun, Xiaoming

doi:10.1016/j.medj.2024.01.006

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…46 The presence of Arg1 has been linked with various healing processes including new blood vessel formation, wound closure, and reducing inflammation, with its skin expression closely tied to reparative outcomes. [46][47][48] We conducted a quantitative assessment of Arg1 + (N2) neutrophilic subpopulations in the wound lesion and determine if HucMSC-Exo could affect their phenotypic balance. After the initial wound, our observations, taking place at 24 hours, showed that around one in three neutrophils in the wound region were Arg1-positive-a percentage that remained unchanged with HucMSC-Exo administration.…”

Section: Discussionmentioning

confidence: 99%

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

Yang,

Xie,

Xia

et al. 2024

IJN

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Background Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes. Methods HucMSC-Exo were isolated via ultracentrifugation and subsequently administered through subcutaneous injection into full-thickness cutaneous wounds in mice. To determine the impact of host neutrophils on the healing effects of HucMSC-Exo in skin injuries, strategies including neutrophil depletion and adoptive transfer were employed. Flow cytometry was used to evaluate the proportion of N2 subtype neutrophils in both normal and diabetic wounds, and the effect of HucMSC-Exo on this proportion was assessed. Furthermore, the mitochondrial metabolic reprogramming driven by HucMSC-Exo during N2 polarization was investigated through JC1 staining, ATP quantification, fatty acid uptake assays, and assessment of FAO-related genes ( Cpt1b, Acadm, and Acadl ). Results Depleting host neutrophils strikingly dampened prohealing effect of HucMSC-Exo on skin injury, while adoptive transfer of bone marrow neutrophils rescued this process. During normal healing process, some neutrophils expressed N2 markers, in contrast, diabetic wounds exhibited a reduced expression of N2 markers. After treatment with HucMSC-Exo, most neutrophils increased the phosphorylation of STAT6, leading to mitochondrial metabolic reprogramming and thus acquired an N2 phenotype. These N2 neutrophils, polarized by HucMSC-Exo, boosted the release of proangiogenic factors, particularly BV8, a myeloid cell-derived proangiogenic factor, and induced angiogenesis thereby favoring tissue restoration. Conclusion This research uniquely demonstrates the identification of N2 neutrophils in skin injury and shows that HucMSC-Exo could skew neutrophils toward N2 phenotype, enhancing our insight into how cells react to HucMSC-Exo.

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Section: Discussionmentioning

confidence: 99%

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

Yang,

Xie,

Xia

et al. 2024

IJN

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Targeting Osteoblast‐Osteoclast Cross‐Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats

Zheng,

Li,

Zhang

et al. 2024

Adv Healthcare Materials

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Balancing osteoblast‐osteoclast (OB‐OC) cross‐talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross‐talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin‐specific protease 26 (USP26) is shown to coordinate OB‐OC cross‐talk by independently regulating β‐catenin and Iκb‐α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA‐loaded lipid nanoparticles (mRNA@LNP) within MMPs‐responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB‐OC cross‐talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell‐to‐cell cross‐talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.

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Engineered nanovesicles mediated cardiomyocyte survival and neovascularization for the therapy of myocardial infarction

Zhang,

Zhang

et al. 2024

Colloids and Surfaces B: Biointerfaces

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Balancing macrophage polarization via stem cell-derived apoptotic bodies for diabetic wound healing

Cited by 3 publications

References 45 publications

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

Targeting Osteoblast‐Osteoclast Cross‐Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats

Engineered nanovesicles mediated cardiomyocyte survival and neovascularization for the therapy of myocardial infarction

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