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Generation of Autologous Vascular Endothelial Cells for Patients with Peripheral Artery Disease

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Abstract

Peripheral artery disease (PAD) is a prevalent cardiovascular disease with risks of limb loss. Our objective is to establish an autologous cell source for vascular regeneration to achieve limb salvage in PAD. Six PAD patients (age 50–80) were enrolled with their peripheral blood collected to derive vascular endothelial cells (ECs) with two different approaches: (1) endothelial progenitor cell (EPC) approach and (2) induced pluripotent stem cell (iPSC) approach. The iPSC approach successfully generated patient-specific ECs for all PAD patients, while the EPC approach did not yield any colony-forming ECs in any of the patients. The patient-derived iPSC-ECs expressed endothelial markers and exhibited endothelial functions. However, elevated inflammatory status with VCAM-1 expression was observed in the patient-derived cells. Pharmacological treatment with resveratrol resulted in patient-specific responses in cell viability and VCAM-1 expression. Our study demonstrates the potential of iPSC-ECs for autologous regenerative therapy in PAD, offering promise for personalized treatments for ischemic PAD.

Graphical Abstract

Our study establishes autologous endothelial cells from induced pluripotent stem cells as a cellular resource for regenerative treatments in peripheral artery disease.

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Abbreviations

ABI:

Ankle brachial index

Ac-LDL:

Acetylated low-density lipoprotein

cGMP:

Current good manufacturing practice

EC:

Endothelial cell

EDTA:

Ethylenediaminetetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

EPC:

Endothelial progenitor cell

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

HRP:

Horseradish peroxidase

iPSC:

Induced pluripotent stem cell

MOI:

Multiplicity of infection

OSKM:

Oct4, Sox2, Klf4, and c-Myc

PAD:

Peripheral artery disease

PBMC:

Peripheral blood mononuclear cell

PBS:

Phosphate buffered saline

rhBMP4:

Recombinant human bone morphogenetic protein 4

rhVEGF:

Recombinant human vascular endothelial growth factor

rhVTN:

Recombinant human vitronectin

ROS:

Reactive oxygen species

VCAM-1:

Vascular cell adhesion molecule 1

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Acknowledgements

We thank Dr. Melina Kibbe and Dr. Karen Ho from Northwestern Memorial Hospital (Chicago, IL) for clinical support throughout the project. We also thank members from the Clinical Research Units of the Northwestern University Clinical and Translational Sciences (NUCATS) Institute for coordination and nursing services. This work was supported by the equipment, training, and services from the Northwestern University RHLCCC Flow Cytometry Facility (Evanston and Chicago, IL) and the Stem Cell Core Facility (Chicago, IL).

Funding

This work is funded by the National Institute of Health (5R01EB017129), the American Heart Association (14POST20160091 and 19TPA34890008), and the Chicago Biomedical Consortium (PDR-008).

Author information

Authors and Affiliations

  1. Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA

    Bin Jiang, Xinlong Wang, Nancy Rivera-Bolanos & Guillermo A. Ameer

  2. Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Rd, Tech B382, Evanston, IL, 60208, USA

    Bin Jiang, Xinlong Wang, Nancy Rivera-Bolanos & Guillermo A. Ameer

  3. Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Bin Jiang & Guillermo A. Ameer

  4. Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, 60208, USA

    Guillermo A. Ameer

  5. International Institute for Nanotechnology, Northwestern University, Evanston, IL, 60208, USA

    Guillermo A. Ameer

  6. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA

    Guillermo A. Ameer

Authors
  1. Bin Jiang
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  2. Xinlong Wang
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  3. Nancy Rivera-Bolanos
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  4. Guillermo A. Ameer
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Corresponding authors

Correspondence to Bin Jiang or Guillermo A. Ameer.

Ethics declarations

Ethics Approval and Consent to Participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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The authors declare no competing interests.

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Associate Editor Nicola Smart oversaw the review of this article

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Jiang, B., Wang, X., Rivera-Bolanos, N. et al. Generation of Autologous Vascular Endothelial Cells for Patients with Peripheral Artery Disease. J. of Cardiovasc. Trans. Res. (2023). https://doi.org/10.1007/s12265-023-10452-z

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  • DOI: https://doi.org/10.1007/s12265-023-10452-z

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