3D migration of human amniotic fluid stem cells involves mesenchymal and amoeboid modes and is regulated by mTORC1
This study on human amniotic fluid stem cells (hAFSCs) provides the first demonstration that human stem cells exhibit mTORC1-dependent invasive capacity and can concurrently make use of mesenchymal and amoeboid 3D cell migration modes. These results represent an important step towards the full biological characterization of fetal human stem cells with relevance to developmental research and stem cell-based therapy. Abstract3D cell migration is an integral part of many physiologic processes. Although being well studied in the context of adult tissue homeostasis and cancer development, remarkably little is known about the in...
Source: Stem Cells - August 1, 2021 Category: Stem Cells Authors: Margit Rosner, Markus Hengstschl äger Tags: Tissue ‐Specific Stem Cells Source Type: research

Human multipotent adult progenitor cells effectively reduce graft ‐vs‐host disease while preserving graft‐vs‐leukemia activity
We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs ™) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models. Injection of MAPC cells on day +1 (D1) and +4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, Tumor Necrosis Factor Alpha (TNFα ) and Interferon Gamma (IFNγ)-producing, CD4+ and CD8+ cells by D10 compared with untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflamm...
Source: Stem Cells - July 28, 2021 Category: Stem Cells Authors: Leland Metheny, Saada Eid, Patiwet Wuttisarnwattana, Jeffery J. Auletta, Chen Liu, Alana Van Dervort, Conner Paez, ZhengHong Lee, David Wilson, Hillard M. Lazarus, Robert Deans, Wouter Vant Hof, Yiouli Ktena, Kenneth R. Cooke Tags: Tissue ‐Specific Stem Cells Source Type: research

A preview of selected articles
(Source: Stem Cells)
Source: Stem Cells - July 28, 2021 Category: Stem Cells Authors: Stuart P. Atkinson Tags: PREVIEWS Source Type: research

Cover Image
Image depicts a potential approach to the perfusion of human brain organoids with an organ-on-chip device. A brain organoid is cultivated in a device with the fluid channels including vascular cells. The vascular cells may migrate and form vessel-like structures that bridge the fluid channel and the brain organoid. This kind of device succeeded in establishing vessel-like structures in the lung fibroblast spheroid.See Matsui et al. beginning on page1017. (Source: Stem Cells)
Source: Stem Cells - July 27, 2021 Category: Stem Cells Tags: COVER IMAGE Source Type: research

Issue Information
(Source: Stem Cells)
Source: Stem Cells - July 27, 2021 Category: Stem Cells Tags: ISSUE INFORMATION Source Type: research

Downregulation of ALR impairs the therapeutic efficacy of LEPCs against acute liver injury by enhancing mitochondrial fission
In conclusion, we demonstrated that the transplantation ofALR-transfected LEPCs protected mice against CCl4-induced ALI, thus offering immense curative potential in the clinic.© AlphaMed Press 2021Significance StatementAugmenter of liver regeneration (ALR) is known to regulate mitochondrial dynamics in hepatocytes, thus offering protection against liver injury. However, whether ALR exerts a similar function in adult liver stem cells, thereby supporting cell transplantation in damaged liver with improved therapeutic efficacy, is not known. The results of the current study demonstrated that ALR was beneficial in LEPCs (live...
Source: Stem Cells - July 27, 2021 Category: Stem Cells Authors: Yuan Dong, Wei ‐ning Kong, Wei An Tags: Tissue ‐Specific Stem Cells Source Type: research

Impaired generation of mature neurons due to extended expression of Tlx by repressing Sox2 transcriptional activity
Without shutting-off on schedule, extended expression of Tailless (Tlx) in neural stem cells (NSCs) and their progenies prevents NSCs from neural maturation by repressing Sox2 transcriptional activity. AbstractAs a master regulator of the dynamic process of adult neurogenesis, timely expression and regulation of the orphan nuclear receptor Tailless (Tlx) is essential. However, there is no study yet to directly investigate the essential role of precise spatiotemporal expressed Tlx. Here, we generated a conditional gain of Tlx expression transgenic mouse model, which allowed the extended Tlx expression in neural stem cells (...
Source: Stem Cells - July 18, 2021 Category: Stem Cells Authors: Yu Wang, Bin Li, Lianwei Dong, Weibing Duan, Anna Neuerburg, Han Zhang, Xijuan Jiang, Rui Shao, Yan Zhu, Dagmar Bock, Erwei Liu, Hong Wang, Yunsha Zhang, Yifan Dai, Haiyuan Yang, Ying Wang Tags: Tissue ‐Specific Stem Cells Source Type: research

Hematopoietic stem cell ‐derived functional osteoblasts exhibit therapeutic efficacy in a murine model of Osteogenesis imperfecta
Transplantation (Tp) of hematopoietic stem cells (HSCs) inOsteogenesis imperfecta (OI) mice causes replacement of mutated osteoblasts with normal osteoblasts (derived from HSCs) that lay down normal collagen and result in clinical improvements. AbstractCurrently, there is no cure forOsteogenesis imperfecta (OI) —a debilitating pediatric skeletal dysplasia. Herein we show that hematopoietic stem cell (HSC) therapy holds promise in treating OI. Using single-cell HSC transplantation in lethally irradiatedoim/oim mice, we demonstrate significant improvements in bone morphometric, mechanics, and turnover parameters. Important...
Source: Stem Cells - July 15, 2021 Category: Stem Cells Authors: In ‐Hong Kang, Uday K. Baliga, Yongren Wu, Shikhar Mehrotra, Hai Yao, Amanda C. LaRue, Meenal Mehrotra Tags: Regenerative Medicine Source Type: research

Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis ‐related genes in mouse embryonic stem cells
MGA bearing two distinct DNA-binding domains is a scaffolding component of PRC1.6 that prevents precocious and ectopic onset of meiosis in germ cells and embryonic stem cells (ESCs), respectively. Here, we demonstrate that both Mga domains repress distinct sets of meiosis-related genes in ESCs. Our data also identifiedMeiosin as a linchpin molecule between positive and negative regulations of meiotic onset. AbstractAlthough the physiological meaning of the high potential of mouse embryonic stem cells (ESCs) for meiotic entry is not understood, a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC...
Source: Stem Cells - July 14, 2021 Category: Stem Cells Authors: Kousuke Uranishi, Masataka Hirasaki, Yuka Kitamura, Yosuke Mizuno, Masazumi Nishimoto, Ayumu Suzuki, Akihiko Okuda Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Prostacyclin is an endosteal bone marrow niche component and its clinical analog iloprost protects hematopoietic stem cell potential during stress
In conclusion, we propose that PGI2 is a novel HSC regulator enriched in the endosteum that promotes HSC regenerative potential following stress.© AlphaMed Press 2021Significance StatementWe discovered prostacyclin as a novel HSC regulator enriched in endosteal bone marrow niches.Ex vivo andin vivo treatment with clinical prostacyclin analogs enhanced HSC reconstitution potential and protect HSC from stress-mediated exhaustion. These findings open new therapeutic avenues to improve HSC engraftment after autologous transplantations by shortex vivo pulse treatment with prostacyclin analogs; and limit loss of HSC and acquire...
Source: Stem Cells - July 14, 2021 Category: Stem Cells Authors: Joshua Tay, Valerie Barbier, Falak M. Helwani, Gareth R. Price, Jean ‐Pierre Levesque, Ingrid G. Winkler Tags: Tissue ‐Specific Stem Cells Source Type: research

Human multipotent adult progenitor cells effectively reduce graft ‐vs‐host disease while preserving graft‐vs‐leukemia activity following experimental, allogeneic bone marrow transplantation
We examined whether the administration of human, bone marrow-derived, multi-potent, adult progenitor cells (MAPC) could regulate experimental GvHD. The immuno-regulatory capacity of MAPC cells was evaluatedin vivo using established murine GvHD models. Injection of MAPC cells on Day +1 (D1) and  + 4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, TNFα and IFNγ-producing, CD4+ and CD8+ cells by D10 compared to untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflammation and syst emic GvHD as measured by survival ...
Source: Stem Cells - July 14, 2021 Category: Stem Cells Authors: Leland Metheny, Saada Eid, Patiwet Wuttisarnwattana, Jeffery J Auletta, Chen Liu, Alana Van Dervort, Conner Paez, Zheng Hong Lee, David Wilson, Hillard M Lazarus, Robert Deans, Vant Hof Wouter, Yiouli Ktena, Kenneth R Cooke Tags: Tissue ‐Specific Stem Cells Source Type: research

Prostacyclin is an endosteal bone marrow niche component and its clinical analog iloprost protects hematopoietic stem cell potential during stress
In conclusion, we propose that PGI2 is a novel HSC regulator enriched in the endosteum that promotes HSC regenerative potential following stress.© AlphaMed Press 2021Significance StatementWe discovered prostacyclin as a novel HSC regulator enriched in endosteal bone marrow niches.Ex vivo andin vivo treatment with clinical prostacyclin analogs enhanced HSC reconstitution potential and protect HSC from stress-mediated exhaustion. These findings open new therapeutic avenues to improve HSC engraftment after autologous transplantations by shortex vivo pulse treatment with prostacyclin analogs; and limit loss of HSC and acquire...
Source: Stem Cells - July 14, 2021 Category: Stem Cells Authors: Joshua Tay, Valerie Barbier, Falak M. Helwani, Gareth R. Price, Jean ‐Pierre Levesque, Ingrid G. Winkler Tags: Tissue ‐Specific Stem Cells Source Type: research

Bone ‐forming perivascular cells: Cellular heterogeneity and use for tissue repair
Mesenchymal progenitor cells in the tunica adventitia have a hierarchy of differentiation and proliferation potential. On top of the hierarchy, platelet-derived growth factor receptor (PDGFR) α+ and aldehyde dehydrogenase (ALDH)High cells show a bipotent differentiation potential into osteogenic and adipogenic cell lineages with high proliferative rate. Conversely, CD10 and CD107a expression separate osteogenic progenitors from adipogenic progenitors, respectively. Moreover, osteoprogenitors can transition into adipogenic phenotype. AbstractMesenchymal progenitor cells are broadly distributed across perivascular niches ...
Source: Stem Cells - July 13, 2021 Category: Stem Cells Authors: Jiajia Xu, Yiyun Wang, Mario A. Gomez ‐Salazar, Ginny Ching‐Yun Hsu, Stefano Negri, Zhao Li, Winters Hardy, Lijun Ding, Bruno Peault, Aaron W. James Tags: Tissue ‐Specific Stem Cells Source Type: research