Extracellular matrix derived from Wharton's Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF.

Angiogenesis is required in many physiological conditions, including bone regeneration, wound healing, and tissue regeneration. Mesenchymal stem cells-derived extracellular matrix (MSCs-ECM) could guide intricate cellular and tissue processes such as homeostasis, healing and regeneration. The purpose of this study is to explore the effect and mechanism of ECM derived from decellularized Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) on endothelial cell viability and angiogenesis. The human umbilical vein endothelial cells (HUVECs) were pretreated with WJ-MSCs ECM for 2d/7d/14d, respectively. After pretreatment, the angiogenesis ability of HUVECs was detected. In this study, we found for the first time that WJ-MSCs ECM could improve the angiogenesis ability of HUVECs with a time-dependent manner in vitro. Mechanically, WJ-MSCs ECM activated the focal adhesion kinase (FAK)/P38 signaling pathway via integrin αVβ3, which further promoted the expression of the cellular (c)-Myc. Further, c-Myc increased histone acetylation levels of the vascular endothelial growth factor (VEGF) promoter by recruiting P300, which ultimately promoting VEGF expression. ECM derived from Wharton's Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF. This study is expected to provide a new approach to promote angiogenesis in bone and tissue regeneration.

Ma B ，Wang T ，Li J ，Wang Q ... -  《Stem Cell Research & Therapy》

Extracellular Vesicle-Derived microRNAs of Human Wharton's Jelly Mesenchymal Stromal Cells May Activate Endogenous VEGF-A to Promote Angiogenesis.

Chinnici CM ，Iannolo G ，Cittadini E ，Carreca AP ，Nascari D ，Timoneri F ，Bella MD ，Cuscino N ，Amico G ，Carcione C ，Conaldi PG ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Netrin-1 acts as a non-canonical angiogenic factor produced by human Wharton's jelly mesenchymal stem cells (WJ-MSC).

Prieto CP ，Ortiz MC ，Villanueva A ，Villarroel C ，Edwards SS ，Elliott M ，Lattus J ，Aedo S ，Meza D ，Lois P ，Palma V ... -  《Stem Cell Research & Therapy》

Human-derived extracellular matrix from Wharton's jelly: An untapped substrate to build up a standardized and homogeneous coating for vascular engineering.

One of the outstanding goals in tissue engineering is to develop a natural coating surface which is easy to manipulate, effective for cell adhesion and fully biocompatible. The ideal surface would be derived from human tissue, perfectly controllable, and pathogen-free, thereby satisfying all of the standards of the health authorities. This paper reports an innovative approach to coating surfaces using a natural extracellular matrix (ECM) extracted from the Wharton's jelly (WJ) of the umbilical cord (referred to as WJ-ECM). We have shown by atomic force microscopy (AFM), that the deposition of WJ-ECM on surfaces is homogenous with a controllable thickness, and that this easily-prepared coating is appropriate for both the adhesion and proliferation of human mesenchymal stem cells and mature endothelial cells. Furthermore, under physiological shear stress conditions, a larger number of cells remained adhered to WJ-ECM than to a conventional coating such as collagen - a result supported by the higher expression of both integrins α2 and β1 in cells cultured on WJ-ECM. Our data clearly show that Wharton's jelly is a highly promising coating for the design of human biocompatible surfaces in tissue engineering as well as in regenerative medicine. Discovery and design of biomaterial surface are a hot spot in the tissue engineering field. Natural matrix is preferred to mimic native cell microenvironment but its use is limited due to poor resource availability. Moreover, current studies often use single or several components of natural polymers, which is not the case in human body. This paper reports a natural extracellular matrix with full components derived from healthy human tissue: Wharton's jelly of umbilical cord. Reconstituting this matrix as a culture surface, our easily-prepared coating provides superior biocompatibility for stem and mature cells. Furthermore, we observed improved cell performance on this coating under both static and dynamic condition. This novel human derived ECM would be a promising choice for regenerative medicine.

Dan P ，Velot É ，Francius G ，Menu P ，Decot V ... -  《-》

Compared to the amniotic membrane, Wharton's jelly may be a more suitable source of mesenchymal stem cells for cardiovascular tissue engineering and clinical regeneration.

Pu L ，Meng M ，Wu J ，Zhang J ，Hou Z ，Gao H ，Xu H ，Liu B ，Tang W ，Jiang L ，Li Y ... -  《Stem Cell Research & Therapy》