Contribution of Adventitia-Derived Stem and Progenitor Cells to New Vessel Formation in Tumors

Küçük Resim Yok

Tarih

2021

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Mdpi

Erişim Hakkı

info:eu-repo/semantics/openAccess

Özet

Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34(+) VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs' adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.

Açıklama

Anahtar Kelimeler

Vascularization Model, Tumor Spheroids, Vascular Wall Stem And Progenitor Cells, Aortic Adventitia, Vasculogenesis, Tumor-Vessel Wall-İnterface Model, Vasculogenic Mimicry, Vascular Adventitia, Angiogenesis, Growth, Spheroids, Induction, Cancer, Identification, Chemokines, Hierarchy

Kaynak

Cells

WoS Q Değeri

Q2

Scopus Q Değeri

Q1

Cilt

10

Sayı

7

Künye