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The mouse lymph node as an ectopic transplantation site for multiple tissues.

ABSTRACT: Cell-based therapy has been viewed as a promising alternative to organ transplantation, but cell transplantation aimed at organ repair is not always possible. Here we show that the mouse lymph node can support the engraftment and growth of healthy cells from multiple tissues. Direct injection of hepatocytes into a single mouse lymph node generated enough ectopic liver mass to rescue the survival of mice with lethal metabolic disease. Furthermore, thymuses transplanted into single lymph nodes of athymic nude mice generated functional immune systems that were capable of rejecting allogeneic and xenogeneic grafts. Additionally, pancreatic islets injected into the lymph nodes of diabetic mice restored normal glucose control. Collectively, these results suggest the practical approach of targeting lymph nodes to restore, maintain or improve tissue and organ functions.

SUBMITTER: Komori J

PROVIDER: S-EPMC3469750 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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The mouse lymph node as an ectopic transplantation site for multiple tissues.

Komori Junji J Boone Lindsey L DeWard Aaron A Hoppo Toshitaka T Lagasse Eric E

Nature biotechnology 20120923 10

Cell-based therapy has been viewed as a promising alternative to organ transplantation, but cell transplantation aimed at organ repair is not always possible. Here we show that the mouse lymph node can support the engraftment and growth of healthy cells from multiple tissues. Direct injection of hepatocytes into a single mouse lymph node generated enough ectopic liver mass to rescue the survival of mice with lethal metabolic disease. Furthermore, thymuses transplanted into single lymph nodes of ...[more]

PMID: 23000933

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Project description:BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).

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The mouse lymph node as an ectopic transplantation site for multiple tissues.

Publications

The mouse lymph node as an ectopic transplantation site for multiple tissues.

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