Progenitor Cell Sources for 3D Bioprinting of Lymphatic Vessels and Potential Clinical Application

Abstract

The lymphatic system maintains tissue fluid homeostasis and it is involved in the transport of nutrients and immunosurveillance. It also plays a pivotal role in both pathological and regenerative processes. Lymphatic development in the embryo occurs by polarization and proliferation of lymphatic endothelial cells from the lymph sacs, that is, lymphangiogenesis. Alternatively, lymphvasculogenesis further contributes to the formation of lymphatic vessels. In adult tissues, lymphatic formation rarely occurs under physiological conditions, being restricted to pathological processes. In lymphvasculogenesis, progenitor cells seem to be a source of lymphatic vessels. Indeed, mesenchymal stem cells, adipose stem cells, endothelial progenitor cells, and colony-forming endothelial cells are able to promote lymphatic regeneration by different mechanisms, such as direct differentiation and paracrine effects. In this review, we summarize what is known on the diverse stem/progenitor cell niches available for the lymphatic system, emphasizing the potential that these cells hold for lymphatic tissue engineering through 3D bioprinting and their translation to clinical application.

Impact statement

The lymphatic system undertakes many physiological functions of the body. Growing evidence suggests it also participates in different pathologies such as cancer metastasis. Lymphangiogenesis is the formation of new lymphatic vessels from pre-existing ones and is mainly limited to embryonic development or pathologic conditions. Conversely, lymphvasculogenesis is described as the formation of new lymphatic vessels from progenitor cells. The origin and formation of lymphatic vessels in the adult remains obscure. This review describes the different stem/progenitor cells niches in the body and their adequacy as cell sources for 3D bioprinting of vessels for lymphatic tissue regeneration.