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Am J Transl Res 2013;5(5):510-520
Original Article
Chemotaxis of human induced pluripotent stem cell-derived
endothelial cells
Ngan F Huang, Ruby E Dewi, Janet Okogbaa, Jerry C Lee, Abdul JalilRufaihah, Sarah C Heilshorn, John P Cooke
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; Department of Materials Science and Engineering, Stanford University, 476
Lomita Mall, Stanford, CA 94305, USA
Received June 28, 2013; Accepted July 15, 2013; Epub August 15, 2013; Published August 30, 2013
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.
(AJTR1306006).
Keywords: Induced pluripotent stem cells, endothelial cells, CXCR4, SDF-1, homing, hindlimb ischemia
Address correspondence to: Dr. John P Cooke, Division of Cardiovascular Medicine, Stanford University, 300
Pasteur Drive, Stanford, CA 94305-5406, USA. Tel: 650-723-6459; Fax: 650-723-8392; E-mail: jcooke@stanford.
edu
Original Article
Chemotaxis of human induced pluripotent stem cell-derived
endothelial cells
Ngan F Huang, Ruby E Dewi, Janet Okogbaa, Jerry C Lee, Abdul JalilRufaihah, Sarah C Heilshorn, John P Cooke
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; Department of Materials Science and Engineering, Stanford University, 476
Lomita Mall, Stanford, CA 94305, USA
Received June 28, 2013; Accepted July 15, 2013; Epub August 15, 2013; Published August 30, 2013
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.
(AJTR1306006).
Keywords: Induced pluripotent stem cells, endothelial cells, CXCR4, SDF-1, homing, hindlimb ischemia
Address correspondence to: Dr. John P Cooke, Division of Cardiovascular Medicine, Stanford University, 300
Pasteur Drive, Stanford, CA 94305-5406, USA. Tel: 650-723-6459; Fax: 650-723-8392; E-mail: jcooke@stanford.
edu
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