Amniotic Mesenchymal Stem Cells Share Similar Angiogenic Capacity With Bone Marrow Mesenchymal Stem Cells

Objectives: To evaluate the angiogenic capacity and proteolytic mechanism of co-culture using human amniotic mesenchymal stem cells (hAMSCs) with human umbilical vein endothelial cells (HUVECs) in vitro and in vivo by comparing to those of co-culture using bone marrow mesenchymal stem cells with HUVECs.
Methods: For the in vivo experiment, cells (HUVEC-monoculture, HUVEC-hAMSC co-culture and HUVEC-BMMSC co-culture) were seeded in fibrin gels and injected subcutaneously in nude mice. The samples were collected on days 7 and 14 and histologically analyzed by hematoxylin-eosin and platelet endothelial cell adhesion molecule (PECAM-1; CD31) staining. CD31-positive staining percentage, Vessel-like structure (VLS) density were evaluated as quantitive parameters for angiogenesis. For the in vitro experiment, we utilized the same 3D culture model to investigate the proteolytic mechanism related to capillary formation by using broad spectrum MMP inhibitor (GM6001).
Results: In vivo, the increase of CD31-positive stained area was found in the comparison of between the two types of co-cultures at the two time points, but significant decrease was found in HUVEC-only group. VLS density of both HUVEC-hAMSC group and HUVEC-BMMSC group at day 14 was obviously higher than that at day 7, while, obvious decline in VLS density was observed for HUVEC-only group between two time points.
In vitro, HUVECs invaded their surrounding matrix, but did not form capillaries. However, HUVECs could form intensive vascular networks associated with hAMSCs or BMMSCs. MMP2 and MMP9 expression in hAMSCs increased significantly in 3D culture condition.The administration of broad spectrum MMP inhibitor (GM6001) restricted the MSC-stimulated capillary formation.
Conclusions: This study demonstrated that hAMSCs shared similar capacity and proteolytic mechanism with BMMSCs on neovascularization.