Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Transl Res. 2013 Aug 15;5(5):510-20. eCollection 2013.

Chemotaxis of human induced pluripotent stem cell-derived endothelial cells.

Author information

1
Division of Cardiovascular Medicine, Stanford University 300 Pasteur Drive, Stanford, CA 94305-5406, USA ; Stanford Cardiovascular Institute, Stanford University 300 Pasteur Drive, Stanford, CA 94305, USA ; Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs Palo Alto Health Care System 3801 Miranda Avenue, Palo Alto, CA 94304, USA.

Abstract

This study examined the homing capacity of human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and their response to chemotactic gradients of stromal derived factor-1α (SDF). We have previously shown that EC derived from murine pluripotent stem cells can home to the ischemic hindlimb of the mouse. In the current study, we were interested to understand if ECs derived from human induced pluripotent stem cells are capable of homing. The homing capacity of iPSC-ECs was assessed after systemic delivery into immunodeficient mice with unilateral hindlimb ischemia. Furthermore, the iPSC-ECs were evaluated for their expression of CXCR4 and their ability to respond to SDF chemotactic gradients in vitro. Upon systemic delivery, the iPSC-ECs transiently localized to the lungs but did not home to the ischemic limb over the course of 14 days. To understand the mechanism of the lack of homing, the expression levels of the homing receptor, CXCR4, was examined at the transcriptional and protein levels. Furthermore, their ability to migrate in response to chemokines was assessed using microfluidic and scratch assays. Unlike ECs derived from syngeneic mouse pluripotent stem cells, human iPSC-ECs do not home to the ischemic mouse hindlimb. This lack of functional homing may represent an impairment of interspecies cellular communication or a difference in the differentiation state of the human iPSC-ECs. These results may have important implications in therapeutic delivery of iPSC-ECs.

KEYWORDS:

CXCR4; Induced pluripotent stem cells; SDF-1; endothelial cells; hindlimb ischemia; homing

PMID:
23977410
PMCID:
PMC3745438
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center