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. 2024 May 16;4(6):100779. doi: 10.1016/j.crmeth.2024.100779

Table 1.

Different cellular sources for generating ECs used for vascularizing organoids and tissue constructs

Cellular source Markers Advantages Bioengineering challenges
HUVECs CD31 (PECAM-1), CD144 (VE-Cadherin), vWF, eNOS
  • 1.

    robust ability to form vessel-like structures in vitro and in vivo

  • 2.

    ease of isolation and characterization

  • 3.

    extensively studied in vascular research

  • 1.

    source variability with differences in genetic and phenotypic characteristics between donors

  • 2.

    limited in vivo functionality long term

  • 3.

    prone to senescence during prolonged culturing

  • 4.

    limited ability to form microvessels

  • 5.

    HUVECs can overexpress inflammatory markers under certain conditions

  • 6.

    ethical concern with supply in some parts of the world

EPCs early EPC markers:
CD34, CD133, VEGFR-2
late EPC markers:
CD31 (PECAM-1), CD144 (VE-Cadherin), vWF, eNOS
  • 1.

    inherent angiogenic capabilities

  • 2.

    ability to home to ischemic sites

  • 3.

    potential for rapid proliferation and maturation into ECs1

  • 1.

    phenotypic heterogeneity due to lack of specific markers

  • 2.

    finite proliferative potential in adult peripheral blood

  • 3.

    challenges in achieving full maturity and function as mature ECs

hPSCs (hiPSCs/hESCs) hPSC-ECs:
CD31 (PECAM-1), CD144 (VE-Cadherin), vWF, eNOS
loss of pluripotency markers:
LIN28, OCT4, NANOG, SOX2, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, UTF1
  • 1.

    patient-specific (hiPSCs) and autologous source for personalized medicine

  • 2.

    versatility in differentiation into both ECs and perivascular cells

  • 3.

    provides a renewable source of cells

  • 4.

    can be precisely modified using the CRISPR-Cas9 system

  • 5.

    physiologically relevant to model inflammatory conditions

  • 1.

    achieving high and consistent yield of hPSC-ECs remains a challenge

  • 2.

    risk of in vivo teratoma formation from residual undifferentiated cells

  • 3.

    reprogramming somatic cells can result in genetic and epigenetic abnormalities

  • 4.

    differentiation protocols are complex and resource intensive

  • 5.

    hPSC-EC populations can be heterogeneous and contain off-target cells

  • 6.

    some hPSC-ECs can be immunogenic

These different cellular sources are characterized by specific surface markers, and each has several advantages and bioengineering challenges associated with its use in vascularization systems.