Feasibility of pedicled vascularized inguinal lymph node transfer in a mouse model: A preliminary study

Ishikawa, Kosuke; Maeda, Taku; Funayama, Emi; Hayashi, Toshihiko; Murao, Naoki; Osawa, Masayuki; Furukawa, Hiroshi; Oyama, Akihiko; Yamamoto, Yuhei

doi:10.1002/micr.30394

Cited by 11 publications

(19 citation statements)

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“…In contrast to previous LN transplantation studies on axillary LNs ( 49 ), popliteal LNs ( 8 ) and inguinal LNs ( 58 ), the use of fibrin glue served as a biological adhesive in our study and supported the engraftment of donor mLNs into the mesenteric tissue. Different nodes of mLNs drain from the jejunum, ileum and the colon ( 17 – 19 ) but in this study we did not elucidated if the orthotopically transplanted mLNs retained the similar lymph drainage pattern of distinct intestinal segments after surgical transplantation.…”

Section: Discussionmentioning

confidence: 71%

Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract

et al. 2021

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Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4+ T cells from FVB/N (H-2q) mice homed to the transplanted mLNs in C57BL/6 (H-2b) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4+ T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII+ CD11c+ myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.

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Section: Discussionmentioning

confidence: 71%

Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract

et al. 2021

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“…Each transferred LN was named as follows: group 1, vascularized LN (VLN); group 2, non‐VLN; and group 3, free non‐vascularized LN (FLN). The sample size was determined based on similar animal studies, as well as our previous experience of pedicled vascularized LNT in a murine model …”

Section: Methodsmentioning

confidence: 99%

“…The procedures followed in group 1 were as described previously . In brief, an inguinal lymph node (ILN)‐bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node (PLN).…”

Section: Methodsmentioning

confidence: 99%

“…In that study, the function of the transplanted LN was affected by the change in HEVs brought about by decreased vascularity, so maintaining vascularization may also be important for regeneration of HEVs to maintain the immune functions of the LN. Accordingly, we evaluated the feasibility of pedicled vascularized LNT in a murine model with a postoperative assessment of lymphatic flow using indocyanine green lymphography …”

Section: Introductionmentioning

confidence: 99%

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Changes in high endothelial venules in lymph nodes after vascularized and nonvascularized lymph node transfer in a murine autograft model

Ishikawa

Funayama

Maeda

et al. 2019

Journal of Surgical Oncology

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Background and objectives Vascularized lymph node transfer (LNT) is gaining popularity in the treatment of lymphedema. However, it is unclear whether the vascularization of transferred lymph nodes (LNs) contributes to functional improvement. High endothelial venules (HEVs) are specialized vessels that allow lymphocytes to enter LNs. In this study, we compared the numbers of HEVs and lymphocytes in LNs after vascularized and nonvascularized LNT. Methods Fifty mice were divided into three groups (group 1, pedicled vascularized LNT; group 2, pedicled nonvascularized LNT; group 3, free nonvascularized LNT). Afferent lymphatic reconnection was confirmed by patent blue staining. The transferred LNs were harvested 4 weeks after surgery. HEVs, B‐cells, and T‐cells were subjected to immunohistochemical staining and quantified. Results Afferent lymphatic reconnection was observed in 13 of 20 transferred LNs in group 1, 11 of 15 in group 2, and 7 of 15 in group 3. The ratio of dilated/total HEVs in transferred LNs with afferent lymphatic reconnection was significantly higher in group 1 than in groups 2 and 3. No significant differences in numbers of B‐cells and T‐cells were found in the transferred LNs. Conclusions We found that more functional HEVs were preserved in cases with successful afferent lymphatic reconnection after vascularized LNT than after nonvascularized LNT.

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“…Until now, to overcome this limitation, VLNT in mice was realized as a pedicle flap harvesting VLNT from inguinal (also called "abdominal") to popliteal in the same paw. [8][9][10][11] We believe that the ipsilateral lymph node transfer can represent a limitation in the performance of a VLNT mouse model for two reasons: (1) in case of a VLNT in a lymphedema paw obtained by irradiation on the limb, reasonably the lymph node to transfer will be damaged, as the irradiation decreases lymphatic reserve by causing depletion of lymphatic vessels and lymphatic endothelial cells as well as promoting soft tissue fibrosis. 12 (2) Given that in mice the inguinal and popliteal lymph nodes both drain lymph from the hind leg, 13 removing the popliteal lymph node and harvesting the ipsilateral inguinal one to transfer it in the popliteal region additionally impairs the lymphatic drainage of the paw, which is not ideal for a VLNT model.…”

mentioning

confidence: 99%

Contralateral Vascularized Lymph Node Transfer: An Optimized Mouse Model

Vottero

Morfoisse

Durré

et al. 2019

J Reconstr Microsurg Open

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Background Vascularized lymph node transfer (VLNT) is one of the surgical options in the treatment of lymphedema, but its mechanism of action has not yet been firmly clarified. In the VLNT mouse models described so far, the lymph node flap is performed between two different sites in the same lymphedematous paw. In this study, we describe an optimized VLNT mouse model using the contralateral paw as donor site, thus removing the bias of transferring a lymph node already damaged by irradiation and/or surgery required to induce lymphedema. Methods A lymphedema was induced on the left posterior paw in four experimental groups of mice (n = 8). Two weeks later, group 1 was the sham one, group 2 underwent a VLNT from the right inguinal region to the left, in group 3 a vascular endothelial growth factor (VEGF)-C sponge was placed alone in the left inguinal region, and in group 4 a VEGF-C sponge was associated to the VLNT. The 32 mice were followed during 3 months. Outcomes included paws volume, skin quality, inflammation in the lymphedematous tissue, and lymphatic network density and function. Results Group 4 displayed significantly higher (p < 0.05) lymphedema regression compared with the other three groups. Conclusions This optimized mouse model of VLNT shows to be handy and effective. It could be exploited to perform further experimental studies about the influence of VLNT on lymphedema. Moreover, the local association between VLNT and biological compounds in this model allows it to be a good preclinical model to identify new potential drugs in lymphedema.

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Feasibility of pedicled vascularized inguinal lymph node transfer in a mouse model: A preliminary study

Cited by 11 publications

References 50 publications

Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract

Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract

Changes in high endothelial venules in lymph nodes after vascularized and nonvascularized lymph node transfer in a murine autograft model

Contralateral Vascularized Lymph Node Transfer: An Optimized Mouse Model

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