Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity
We present a new class of agonistic immune checkpoint engagers that protect human leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived endothelial cells (iECs) from innate immune cells. Engagers with agonistic functionality to their inhibitory receptors TIM3 and SIRPα effectively protect engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPα engager can be combined with truncated CD64 to generate fully immune evasive iECs capable of escaping allogeneic cellular and immunoglobulin G (IgG) antibody-mediated rejection. Synthetic immune checkpoint engagers have high target specifici...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Alessia Gravina Grigol Tediashvili Yueting Zheng Kumiko A Iwabuchi Sara M Peyrot Susan Z Roodsari Lauren Gargiulo Shin Kaneko Mitsujiro Osawa Sonja Schrepfer Tobias Deuse Source Type: research

Hiding from allogeneic NK cells and macrophages by a synthetic receptor
Cell Stem Cell. 2023 Nov 2;30(11):1393-1394. doi: 10.1016/j.stem.2023.10.005.ABSTRACTImmune attack by natural killer (NK) cells is a major hurdle for allogeneic off-the-shelf cell therapy, especially when HLA molecules are removed. Gravina et al.1 utilized a membrane-anchored single-chain antibody (scFv) as a synthetic receptor, named "synthetic immune checkpoint engager," to prevent attack from NK cells and macrophages.PMID:37922874 | DOI:10.1016/j.stem.2023.10.005 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Akitsu Hotta Joseph Lee Source Type: research

Meningeal lymphatics stem cognitive decline in craniosynostosis
Cell Stem Cell. 2023 Nov 2;30(11):1395-1397. doi: 10.1016/j.stem.2023.10.004.ABSTRACTCraniosynostosis is a congenital craniofacial disorder where premature fusion of cranial sutures causes elevated intracranial pressure and neurological deficits. In this issue of Cell Stem Cell, Ma et al. demonstrate that replenishing skull progenitor cells alleviates intracranial pressure elevations in craniosynostosis by restoring the meningeal lymphatic system, improving neurocognitive function.PMID:37922875 | DOI:10.1016/j.stem.2023.10.004 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Taylor J Stevenson Kate Hitpass Romero Justin Rustenhoven Source Type: research

Multilineage circuits of regenerative cell states
Cell Stem Cell. 2023 Nov 2;30(11):1397-1399. doi: 10.1016/j.stem.2023.10.006.ABSTRACTRegenerating the lungs' architecture after injury requires rebuilding its fibroelastic extracellular matrix scaffold. Konkimalla et al. establish that regenerative cell states (RCSs) of both epithelial and mesenchymal origin are functionally linked and indispensable for this process. Experimental ablation of RCSs causes organ degeneration, whereas their induction causes organ fibrosis.PMID:37922876 | DOI:10.1016/j.stem.2023.10.006 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Janine Gote-Schniering Herbert B Schiller Source Type: research

Epitope base editing: Non-malignant stem cells are going undercover
Cell Stem Cell. 2023 Nov 2;30(11):1400-1402. doi: 10.1016/j.stem.2023.09.009.ABSTRACTEngineered hematopoietic stem cells can be shielded from targeted immunotherapy. Recently published in Nature, Casirati et al. utilized single-base editing of epitopes implicated in acute myeloid leukemia and healthy hematopoiesis to alter their antibody and chimeric antigen receptor (CAR) T recognition while preserving their ligand binding and enzymatic function.PMID:37922877 | DOI:10.1016/j.stem.2023.09.009 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Shayan Saniei Elvin Wagenblast Source Type: research

Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon
Cell Stem Cell. 2023 Nov 2;30(11):1434-1451.e9. doi: 10.1016/j.stem.2023.10.002.ABSTRACTMost organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembl...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Jorge O M únera Daniel O Kechele Carine Bouffi Na Qu Ran Jing Pritiprasanna Maity Jacob R Enriquez Lu Han Ian Campbell Maxime M Mahe Heather A McCauley Xinghao Zhang Nambirajan Sundaram Jonathan R Hudson Adrian Zarsozo-Lacoste Suman Pradhan Kentaro Tomin Source Type: research

Transitional cell states sculpt tissue topology during lung regeneration
Cell Stem Cell. 2023 Nov 2;30(11):1486-1502.e9. doi: 10.1016/j.stem.2023.10.001.ABSTRACTOrgan regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusive. Here, using multiple injury models, we find that alveolar fibroblasts acquire distinct states marked by Sfrp1 and Runx1 that influence tissue remodeling and reorganization. Unexpectedly, ablation of alveolar epithelial type-1 (AT1) cells alone is sufficient to induce tissue remodel...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Arvind Konkimalla Satoshi Konishi Lauren Macadlo Yoshihiko Kobayashi Zachary J Farino Naoya Miyashita L éa El Haddad Jeremy Morowitz Christina E Barkauskas Pankaj Agarwal Tomokazu Souma Mai K ElMallah Aleksandra Tata Purushothama Rao Tata Source Type: research

Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity
We present a new class of agonistic immune checkpoint engagers that protect human leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived endothelial cells (iECs) from innate immune cells. Engagers with agonistic functionality to their inhibitory receptors TIM3 and SIRPα effectively protect engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPα engager can be combined with truncated CD64 to generate fully immune evasive iECs capable of escaping allogeneic cellular and immunoglobulin G (IgG) antibody-mediated rejection. Synthetic immune checkpoint engagers have high target specifici...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Alessia Gravina Grigol Tediashvili Yueting Zheng Kumiko A Iwabuchi Sara M Peyrot Susan Z Roodsari Lauren Gargiulo Shin Kaneko Mitsujiro Osawa Sonja Schrepfer Tobias Deuse Source Type: research

Hiding from allogeneic NK cells and macrophages by a synthetic receptor
Cell Stem Cell. 2023 Nov 2;30(11):1393-1394. doi: 10.1016/j.stem.2023.10.005.ABSTRACTImmune attack by natural killer (NK) cells is a major hurdle for allogeneic off-the-shelf cell therapy, especially when HLA molecules are removed. Gravina et al.1 utilized a membrane-anchored single-chain antibody (scFv) as a synthetic receptor, named "synthetic immune checkpoint engager," to prevent attack from NK cells and macrophages.PMID:37922874 | DOI:10.1016/j.stem.2023.10.005 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Akitsu Hotta Joseph Lee Source Type: research

Meningeal lymphatics stem cognitive decline in craniosynostosis
Cell Stem Cell. 2023 Nov 2;30(11):1395-1397. doi: 10.1016/j.stem.2023.10.004.ABSTRACTCraniosynostosis is a congenital craniofacial disorder where premature fusion of cranial sutures causes elevated intracranial pressure and neurological deficits. In this issue of Cell Stem Cell, Ma et al. demonstrate that replenishing skull progenitor cells alleviates intracranial pressure elevations in craniosynostosis by restoring the meningeal lymphatic system, improving neurocognitive function.PMID:37922875 | DOI:10.1016/j.stem.2023.10.004 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Taylor J Stevenson Kate Hitpass Romero Justin Rustenhoven Source Type: research

Multilineage circuits of regenerative cell states
Cell Stem Cell. 2023 Nov 2;30(11):1397-1399. doi: 10.1016/j.stem.2023.10.006.ABSTRACTRegenerating the lungs' architecture after injury requires rebuilding its fibroelastic extracellular matrix scaffold. Konkimalla et al. establish that regenerative cell states (RCSs) of both epithelial and mesenchymal origin are functionally linked and indispensable for this process. Experimental ablation of RCSs causes organ degeneration, whereas their induction causes organ fibrosis.PMID:37922876 | DOI:10.1016/j.stem.2023.10.006 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Janine Gote-Schniering Herbert B Schiller Source Type: research

Epitope base editing: Non-malignant stem cells are going undercover
Cell Stem Cell. 2023 Nov 2;30(11):1400-1402. doi: 10.1016/j.stem.2023.09.009.ABSTRACTEngineered hematopoietic stem cells can be shielded from targeted immunotherapy. Recently published in Nature, Casirati et al. utilized single-base editing of epitopes implicated in acute myeloid leukemia and healthy hematopoiesis to alter their antibody and chimeric antigen receptor (CAR) T recognition while preserving their ligand binding and enzymatic function.PMID:37922877 | DOI:10.1016/j.stem.2023.09.009 (Source: Cell Stem Cell)
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Shayan Saniei Elvin Wagenblast Source Type: research

Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon
Cell Stem Cell. 2023 Nov 2;30(11):1434-1451.e9. doi: 10.1016/j.stem.2023.10.002.ABSTRACTMost organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembl...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Jorge O M únera Daniel O Kechele Carine Bouffi Na Qu Ran Jing Pritiprasanna Maity Jacob R Enriquez Lu Han Ian Campbell Maxime M Mahe Heather A McCauley Xinghao Zhang Nambirajan Sundaram Jonathan R Hudson Adrian Zarsozo-Lacoste Suman Pradhan Kentaro Tomin Source Type: research

Transitional cell states sculpt tissue topology during lung regeneration
Cell Stem Cell. 2023 Nov 2;30(11):1486-1502.e9. doi: 10.1016/j.stem.2023.10.001.ABSTRACTOrgan regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusive. Here, using multiple injury models, we find that alveolar fibroblasts acquire distinct states marked by Sfrp1 and Runx1 that influence tissue remodeling and reorganization. Unexpectedly, ablation of alveolar epithelial type-1 (AT1) cells alone is sufficient to induce tissue remodel...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Arvind Konkimalla Satoshi Konishi Lauren Macadlo Yoshihiko Kobayashi Zachary J Farino Naoya Miyashita L éa El Haddad Jeremy Morowitz Christina E Barkauskas Pankaj Agarwal Tomokazu Souma Mai K ElMallah Aleksandra Tata Purushothama Rao Tata Source Type: research

Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity
We present a new class of agonistic immune checkpoint engagers that protect human leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived endothelial cells (iECs) from innate immune cells. Engagers with agonistic functionality to their inhibitory receptors TIM3 and SIRPα effectively protect engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPα engager can be combined with truncated CD64 to generate fully immune evasive iECs capable of escaping allogeneic cellular and immunoglobulin G (IgG) antibody-mediated rejection. Synthetic immune checkpoint engagers have high target specifici...
Source: Cell Stem Cell - November 3, 2023 Category: Stem Cells Authors: Alessia Gravina Grigol Tediashvili Yueting Zheng Kumiko A Iwabuchi Sara M Peyrot Susan Z Roodsari Lauren Gargiulo Shin Kaneko Mitsujiro Osawa Sonja Schrepfer Tobias Deuse Source Type: research