Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models

Kennedy, Crystal C.; Brown, Erin; Abutaleb, Nadia; Truskey, George A.

doi:10.3389/fcvm.2021.625016

Cited by 25 publications

(19 citation statements)

References 132 publications

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“…In addition to ETV2, alteration of the other transcriptional factors such as GATA-2, LMO-2, and TAL-1 have been proposed as a strategy for endothelial differentiation of stem cells ( Elcheva et al, 2014 ; Lange et al, 2020 ). After endothelial differentiation, endothelial-specific markers such as CD31, CD34, CD144, VEGFR-2, and vWF have been used for confirming the endothelial differentiation of stem cells ( Kennedy et al, 2021 ). There are still several questions regarding the functionality of endothelial cells differentiated from hiPSCs.…”

Section: Endothelial Lineage Cellsmentioning

confidence: 99%

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

Shafiee

Shariatzadeh

Zafari

et al. 2021

Front. Bioeng. Biotechnol.

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Currently, the fabrication of a functional vascular network to maintain the viability of engineered tissues is a major bottleneck in the way of developing a more advanced engineered construct. Inspired by vasculogenesis during the embryonic period, the in vitro prevascularization strategies have focused on optimizing communications and interactions of cells, biomaterial and culture conditions to develop a capillary-like network to tackle the aforementioned issue. Many of these studies employ a combination of endothelial lineage cells and supporting cells such as mesenchymal stem cells, fibroblasts, and perivascular cells to create a lumenized endothelial network. These supporting cells are necessary for the stabilization of the newly developed endothelial network. Moreover, to optimize endothelial network development without impairing biomechanical properties of scaffolds or differentiation of target tissue cells, several other factors, including target tissue, endothelial cell origins, the choice of supporting cell, culture condition, incorporated pro-angiogenic factors, and choice of biomaterial must be taken into account. The prevascularization method can also influence the endothelial lineage cell/supporting cell co-culture system to vascularize the bioengineered constructs. This review aims to investigate the recent advances on standard cells used in in vitro prevascularization methods, their co-culture systems, and conditions in which they form an organized and functional vascular network.

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Section: Endothelial Lineage Cellsmentioning

confidence: 99%

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

Shafiee

Shariatzadeh

Zafari

et al. 2021

Front. Bioeng. Biotechnol.

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“…In vitro-cultured ECs have been widely used to model vascular pathology, uncover novel drug targets, and develop promising cell therapies [ 3 – 6 ], e.g., vascular and heart valve tissue engineering [ 6 – 8 ]. The huge value of ECs in basic research and clinical applications demands the production of scalable quantities of the well-defined ECs in laboratory.…”

Section: Introductionmentioning

confidence: 99%

Generation of individualized immunocompatible endothelial cells from HLA-I-matched human pluripotent stem cells

Song

Wang

et al. 2022

Stem Cell Res Ther

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Background Endothelial cells (ECs) derived from human-induced pluripotent stem cell (iPSC) are a valuable cell resource for cardiovascular regeneration. To avoid time-consuming preparation from primary autologous cells, the allogeneic iPSC-ECs are being expected to become “off-the-shelf” cell products. However, allorejection caused by HLA mismatching is a major barrier for this strategy. Although the “hypoimmunogenic” iPSCs could be simply generated by inhibition of HLA-I expression via β-2 microglobulin knockout (B2M KO), the deletion of HLA-I expression will activate natural killer (NK) cells, which kill the HLA-I negative cells. To inhibit NK activation, we proposed to generate HLA-matched iPSCs based on patient’s HLA genotyping by HLA exchanging approach to express the required HLA allele. Methods To establish a prototype of HLA exchanging system, the expression of HLA-I molecules of iPSCs was inhibited by CRISPR/Cas9-mediated B2M KO, and then HLA-A*11:01 allele, as a model molecule, was introduced into B2M KO iPSCs by lentiviral gene transfer. HLA-I-modified iPSCs were tested for their pluripotency and ability to differentiate into ECs. The stimulation of iPSC-EC to allogeneic T and NK cells was detected by respective co-culture of PBMC-EC and NK-EC. Finally, the iPSC-ECs were used as the seeding cells to re-endothelialize the decellularized valves. Results We generated the iPSCs only expressed one HLA-A allele (HLA-A *11:01) by B2M KO plus HLA gene transfer. These HLA-I-modified iPSCs maintained pluripotency and furthermore were successfully differentiated into functional ECs assessed by tube formation assay. Single HLA-A*11:01-matched iPSC-ECs significantly less induced the allogeneic response of CD8+ T cell and NK cells expressing matched HLA-A*11:01 and other HLA-A,-B and -C alleles. These cells were successfully used to re-endothelialize the decellularized valves. Conclusions In summary, a simple HLA-I exchanging system has been created by efficient HLA engineering of iPSCs to evade both of the alloresponse of CD8+ T cells and the activation of NK cells. This technology has been applied to generate iPSC-ECs for the engineering of cellular heart valves. Our strategy should be extremely useful if the “off-the-shelf” and “non-immunogenic” allogeneic iPSCs were created for the common HLA alleles.

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“…Endothelial cells derived from many cell sources through numerous protocols can be potentially delivered for regenerative medicine in patients with cardiovascular disease. In the literature, there are several papers with production protocols of ECFCs using hESCs or hiPSCs [5,[7][8][9]. To our knowledge, we are the first to propose a new valuable source of endothelial cells similar to ECFCs from characterized human stem cells that are not hESCs, hiPSCs or hemangioma stem cells.…”

Section: To the Editormentioning

confidence: 99%

Human CD34+ very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid

et al. 2022

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Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models

Cited by 25 publications

References 132 publications

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

Generation of individualized immunocompatible endothelial cells from HLA-I-matched human pluripotent stem cells

Human CD34+ very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid

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