Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Knoedler, Leonard; Knoedler, Samuel; Lee, Catherine A. A.; Sadigh, Sam; Huelsboemer, Lioba; Stoegner, Viola A.; Kern, Barbara; Mookerjee, Vikram G.; Lian, Christine G.; Tullius, Stefan G.; Murphy, Gëorge F.; Pomahač, Bohdan; Kauke, Martin

doi:10.3389/fimmu.2023.1179355

Cited by 11 publications

(22 citation statements)

References 214 publications

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“…For allograft survival, it is necessary that patients receive highly toxic but effective immunosuppressants, such as tacrolimus, mycophenolate mofetil (MMF), and steroids. Despite this, acute rejection of the skin portion of the allograft occurs in more than 85% of VCA patients within the first year and often multiple times thereafter [ 172 , 173 ]. Given the non-life-saving nature of this procedure, it is particularly important to search for novel avenues that optimize the risk–benefit ratio of VCAs.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cells in skin regeneration and wound healing

Knoedler,

Kauke-Navarro

et al. 2023

Military Med Res

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As the body’s integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality. To this end, multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue. Such temporally- and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation. In this context, regulatory T cells (Tregs) hold a key role in balancing immune homeostasis and mediating cutaneous wound healing. A comprehensive understanding of Tregs’ multifaceted field of activity may help decipher wound pathologies and, ultimately, establish new treatment modalities. Herein, we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair. Further, we discuss how Tregs operate during fibrosis, keloidosis, and scarring.

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Section: Discussionmentioning

confidence: 99%

Regulatory T cells in skin regeneration and wound healing

Knoedler,

Kauke-Navarro

et al. 2023

Military Med Res

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“…Third, unlike the PAT graft that is implanted inside the body under sterile conditions, the skin graft is exposed directly to environmental factors (e.g., dust, urine, feces, and feces microflora, pathogens) and other physical stimuli, which may affect the graft survival and local immune reactions. 34 .…”

Section: Discussionmentioning

confidence: 99%

Modeling human anti‐pig xenoimmune responses in a pig artery tissue grafted humanized mouse model

Fang,

Zou,

et al. 2023

Xenotransplantation

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BackgroundBlood vessels that contain endothelial cells (ECs) on the surface are in direct contact with host blood and are the first target of xenograft rejection. Currently, our understanding of human anti‐pig vessel immune responses is primarily based on in vitro assays using pig ECs. Therefore, it is necessary to develop an animal model that permits in vivo study of human immunological rejection of pig vessels.MethodsPig artery tissues (PAT) were transplanted into human immune system (HIS) mice or immunodeficient NSG mice (as controls). Intragraft human immune cell infiltration and antibody deposition were quantified using histology and immunohistochemistry. Donor antigen‐specific immune responses were quantified using a mixed lymphocyte reaction and a complement‐dependent killing assay.ResultsPig CD31+ ECs were detected and increased 2‐fold from weeks 3 to 5 in PAT xenografts from immunodeficient NSG mice. However, compared with NSG mice, PAT xenografts in HIS mice had significantly lower numbers of porcine CD31+ ECs and showed a marked reduction from week 3 to week 5. PAT xenograft rejection in HIS mice is associated with intensive infiltration of human immune cells, deposition of human IgM and IgG antibodies, and the formation of a tertiary lymphoid structure. Robust donor pig antigen‐specific human T cells and antibody responses were detected in PAT‐transplanted HIS mice.ConclusionWe have developed a humanized mouse model to evaluate human anti‐pig xenoimmune responses by PAT transplantation in vivo. This model is expected to facilitate the refinement of pig gene‐editing strategies (the expression on EC surface) and the testing of local immunosuppressive strategies for clinical pig organ xenotransplantation.

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“…Across various medical fields, increasing understanding of the genetic landscape and cellular pathways holds the potential to facilitate the development of more precise therapies. This can lead to a reduction in off-site effects while enhancing the effectiveness of targeted treatments [63].…”

Section: Discussionmentioning

confidence: 99%

Histomorphometry of the Sural Nerve for Use as a CFNG in Facial Reanimation Procedures

Kehrer

Hollmann

Klein

et al. 2023

JCM

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Facial palsy (FP) is a debilitating nerve pathology. Cross Face Nerve Grafting (CFNG) describes a surgical technique that uses nerve grafts to reanimate the paralyzed face. The sural nerve has been shown to be a reliable nerve graft with little donor side morbidity. Therefore, we aimed to investigate the microanatomy of the sural nerve. Biopsies were obtained from 15 FP patients who underwent CFNG using sural nerve grafts. Histological cross-sections were fixated, stained with PPD, and digitized. Histomorphometry and a validated software-based axon quantification were conducted. The median age of the operated patients was 37 years (5–62 years). There was a significant difference in axonal capacity decrease towards the periphery when comparing proximal vs. distal biopsies (p = 0.047), while the side of nerve harvest showed no significant differences in nerve caliber (proximal p = 0.253, distal p = 0.506) and axonal capacity for proximal and distal biopsies (proximal p = 0.414, distal p = 0.922). Age did not correlate with axonal capacity (proximal: R = −0.201, p = 0.603; distal: R = 0.317, p = 0.292). These novel insights into the microanatomy of the sural nerve may help refine CFNG techniques and individualize FP patient treatment plans, ultimately improving overall patient outcomes.

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Cellular activation pathways and interaction networks in vascularized composite allotransplantation

Cited by 11 publications

References 214 publications

Regulatory T cells in skin regeneration and wound healing

Regulatory T cells in skin regeneration and wound healing

Modeling human anti‐pig xenoimmune responses in a pig artery tissue grafted humanized mouse model

Histomorphometry of the Sural Nerve for Use as a CFNG in Facial Reanimation Procedures

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