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. 2021 Oct 8;22(19):10890. doi: 10.3390/ijms221910890

Table 2.

Summary of in vitro studies involving co-culture of ASCs and endothelial cells to promote vascularization.

EC Type Source of ASC Authors Details and Effect on Vessel Formation
HUVEC Human [8] Culturing of fibrin-embedded spheroids induced organization into prevascular-like structures expressing CD34 and α-SMA.
OEC Human [72] Induced formation of CD31-positive branching vessel structures in a fibrin matrix. Expression of MMP-14 in the invading sprouts. Elevated VEGF secretion.
HUVEC Human [75] Improved capillary network formation and expression of CD31, vWf, VEGF and MMPs in HA/gelatin gel. Enhanced vascularization in a 3D-printed composite scaffold.
AT-EC Human [10] Vascular network with continuous endothelial lumen formation.
HUVEC Human [76] Induced formation of vessel-like structures on Thermanox (2D) and in collagen gel (3D).
BEC + LEC Human [77] In a triculture in fibrin gel, LEC and BEC form separate networks, which are dependent on ASC contact. Lymphatic network is dependent on VEGF-C.
HUVEC, rat LMEC Rat [78] Improved tubulogenesis in Matrigel. Upregulation of VEGF, Ang-2, VEGFR2 and Tie-2 in HUVECs.
EPC, HUVEC Human [21] Increased VEGF secretion and formation of capillary-like structures with longer sprouts in ASC/EPC co-culture but not in ASC/HUVEC co-culture. Blockade of VEGFR2 inhibits capillary-like structure formation.
HUVEC Human [79] Enhanced calcium deposition and secretion of BMP-2 and VEGF, which were further increased by electrical stimulation.
CBD-EC Human [9] The co-culture induces activin A expression in ASCs and secretes lower levels of angiogenic factors compared with ASC culture.
HMEC Human [80] Improved capillary network by osteodifferentiating ASCs. ECs enhance the production of VEGF, PDGF-B and FGF-2 in osteodifferentiating ASCs.
HUVEC, OEC Human [69] Proximity of ASCs required for mature network formation in fibrin gel. ASCs induce and stabilize EC networks by developing pericyte characteristics and by protein secretion.
HUVEC Human [70] Induced network formation and deposition of basal lamina components in a co-culture in fibrin. ASCs differentiate toward a pericyte phenotype.
HUVEC Human [73] ASCs show pericyte-like behavior and differentiation into ECs in a co-culture over a porous membrane.
HUVEC Human [74] ASCs exhibit EC-like phenotype in a co-culture in nitric-oxide-releasing gel. Increased sprouting in the beginning of cultures.
HAMEC, HUVEC Human [22] HAMEC/ASC co-culture induces the most organized and complex vascular network expressing CD31 and α-SMA in a 3D scaffold.
Mouse BMEC Mouse [71] IGF-1 enhances the formation of vessel-like structures and upregulates the expression of angiogenic factors via PI3K/AKT pathway in collagen gel.
HUVEC Human [81] Indirect flow enhances EC sprouting but fails to form vascular networks in fibrin gel, while direct flow inhibits prevascular network formation.
HUVEC Human [82] Pre-culture of ASCs in EGM-2 improves the formation of tube-like structures in a co-culture.
HUVEC Rat [83] Enhanced CD31 expression on co-spun nanofiber substrate.
ECFC Human [84] Co-culture in a hyaluronic acid gel reverses late-passage ASC senescence and shows increased amount of CD31-positive cells.
HDMEC Human [85] Myofibroblast differentiation of ASCs attenuated in co-culture. Hypoxia increases expression of IL-6. Increased expression of VEGF compared with EC culture.