Networked lymphatic endothelial cells in a transplanted cell sheet contribute to form functional lymphatic vessels

Abstract

This study evaluated whether cell sheets containing a network of lymphatic endothelial cells (LECs) promoted lymphangiogenesis after transplantation in vivo. Cell sheets with a LEC network were constructed by co-culturing LECs and adipose-derived stem cells (ASCs) on temperature-responsive culture dishes. A cell ratio of 3:2 (vs. 1:4) generated networks with more branches and longer branch lengths. LEC-derived lymphatic vessels were observed 2 weeks after transplantation of a three-layered cell sheet construct onto rat gluteal muscle. Lymphatic vessel number, diameter and depth were greatest for a construct comprising two ASC sheets stacked on a LEC/ASC (3:2 ratio) sheet. Transplantation of this construct in a rat model of femoral lymphangiectomy led to the formation of functional lymphatic vessels containing both transplanted and host LECs. Further development of this technique may lead to a new method of promoting lymphangiogenesis.

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention

“…All of the above can be evaluated in the current model, provided their dimensions are tailored to fit the missing lymphatic routes. Lymphangiogenesis can also be stimulated by other bioengineering constructs such as cell-only constructs or sheets ( 40 ) or silicone microgroove templates ( 25 ). If scaled up, these materials can be potentially evaluated in the current lymphedema model.…”