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bioRxiv · 10.1101/2023.06.10.544480

Spatiotemporal Transcriptomes of Pig Hearts Reveal Midkine-Mediated Vascularization in a Chronic Myocardial Infarcted Model

Adusumalli, S.·Lim, S.·Ren, V.·Chong, L. Y.·Tham, R.·Ye, L.·Wang, Y.·Petretto, E.·Tryggvason, K.·Yap, L.
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Abstract

Ischemic heart disease is the most prevalent cause of death globally. Regenerative cardiology using stem cell-based therapy is a potential approach to replace infarcted myocardial (MI) heart tissue. We used cardiovascular progenitors (CVPs) derived from human pluripotent embryonic stem cells differentiated to cardiomyocyte progenitors on a laminin 521+221 matrix and transplanted them into acute and chronic MI pig hearts (AMI and CMI). We performed time-series spatial transcriptomics to characterize these human cells at AMI 1- and 2- and at CMI 1-, 4- and 12 weeks post-transplantation. Both models showed high transcriptional reproducibility in the replicates. Furthermore, the human grafts engrafted well, matured, and expressed metabolic, ribosomal, T-tubule, and channel-related genes in the human graft over time. Cell-cell communication analysis revealed Midkine (MDK) signaling as a key pathway that may lead to increased angiogenesis of collaterals in the human graft.

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Adusumalli, S., Lim, S., Ren, V., Chong, L. Y., Tham, R., Ye, L., Wang, Y., Petretto, E., Tryggvason, K., Yap, L.. 2023-06-11. Spatiotemporal Transcriptomes of Pig Hearts Reveal Midkine-Mediated Vascularization in a Chronic Myocardial Infarcted Model. https://doi.org/10.1101/2023.06.10.544480

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