Tissue-engineered lymph node transplantation for the treatment of lymphedema
Catherine L. Ly, MD, Raghu P. Kataru, PhD, Babak J. Mehrara, MD.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
BACKGROUND: Autologous lymph node transplantation (LNT) has been shown to be a promising treatment option for select patients with lymphedema, but is limited by the risk of donor-site complications, particularly iatrogenic donor-site lymphedema. Techniques such as reverse lymphatic mapping have been used to identify lymph nodes that may be harvested with less disruption to the lymphatic vasculature, but no method can completely eliminate the risk of lymphedema. The development of tissue-engineered lymph nodes to avoid the need to harvest donor lymph nodes for LNT is, therefore, an important research goal.
METHODS: Lymph nodes were harvested from adult wild-type mice and decellularized with 0.075% sodium dodecyl sulfate to use as scaffolds for tissue-engineered lymph nodes. The scaffolds were reconstituted with a 1:1 mixture of lymphotoxin alpha (LTα)-transfected thymic stromal cells (TSCs) and mature dendritic cells (DCs) to promote recapitulation of the normal lymph node architecture following transplantation. To determine the effectiveness of these tissue-engineered lymph nodes, a separate set of wild-type mice underwent bilateral popliteal lymph node dissection (PLND) followed by transplantation with a decellularized lymph node on one side and a tissue-engineered lymph node on the other. Four weeks later, near-infrared lymphangiography with indocyanine green (ICG) was used to assess connection to the lymphatic vasculature and lymphatic pumping function.
RESULTS: Tissue-engineered lymph nodes transplanted into the popliteal fossa following PLND were capable of reconnection to the lymphatic vasculature, as indicated by the accumulation of ICG within the lymph nodes following injection into the distal dorsal hindpaw. LNT with these tissue-engineered lymph nodes also promoted the development of collateral lymphatic vessels and slow, but consistent lymphatic pumping function. In contrast, we found that similarly transplanted un-reconstituted decellularized lymph nodes did not connect to the lymphatic vasculature, did not promote lymphangiogenesis, and were associated with irregular, low-amplitude contractions.
CONCLUSIONS: The reconstitution of decellularized lymph node scaffolds with LTα-transfected TSCs and mature DCs for orthotopic LNT into mice that have undergone PLND results in the production of functional lymph node-like structures. Additional research is necessary to further study the effect of LNT with these tissue-engineered lymph nodes and to optimize the process. However, these findings are promising, as they indicate that it may be possible to take advantage of the benefits of LNT without the risk of donor-site complications.
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