Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells.


:Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.


Cell Stem Cell


Cell stem cell


Ye L,Chang YH,Xiong Q,Zhang P,Zhang L,Somasundaram P,Lepley M,Swingen C,Su L,Wendel JS,Guo J,Jang A,Rosenbush D,Greder L,Dutton JR,Zhang J,Kamp TJ,Kaufman DS,Ge Y,Zhang J




Has Abstract


2014-12-04 00:00:00














  • Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus.

    abstract::Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Encinas JM,Michurina TV,Peunova N,Park JH,Tordo J,Peterson DA,Fishell G,Koulakov A,Enikolopov G

    更新日期:2011-05-06 00:00:00

  • Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells.

    abstract::Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs). Using two genetic lineage-tracing systems, we demonstrate the generation of iPSC lines from human pancreatic islet beta cells. These reprogrammed cells acquired markers of pluripotent cells and differentiat...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Bar-Nur O,Russ HA,Efrat S,Benvenisty N

    更新日期:2011-07-08 00:00:00

  • ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation.

    abstract::The Adenomatous Polyposis Coli (APC) gene is mutated in the majority of colorectal cancers (CRCs). Loss of APC leads to constitutively active WNT signaling, hyperproliferation, and tumorigenesis. Identification of pathways that facilitate tumorigenesis after APC loss is important for therapeutic development. Here, we ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Myant KB,Cammareri P,McGhee EJ,Ridgway RA,Huels DJ,Cordero JB,Schwitalla S,Kalna G,Ogg EL,Athineos D,Timpson P,Vidal M,Murray GI,Greten FR,Anderson KI,Sansom OJ

    更新日期:2013-06-06 00:00:00

  • Pluripotent stem cells from cloned human embryos: success at long last.

    abstract::Recently in Cell, Mitalipov and colleagues report an advance that has eluded scientists for over a decade-the successful derivation of embryonic stem cell lines using somatic cell nuclear transfer, or SCNT (Tachibana et al., 2013). ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Trounson A,DeWitt ND

    更新日期:2013-06-06 00:00:00

  • The race for regeneration: Pluripotent-stem-cell-derived 3D kidney structures.

    abstract::The kidney's complex spatial organization and poorly defined lineage specification programs have impeded derivation of kidney progenitors from pluripotent stem cells (PSCs). Now in Cell Stem Cell, Taguchi et al. (2014) redefine the identity of embryonic kidney progenitors in vivo to obtain PSC-derived kidney progenito...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Gouon-Evans V

    更新日期:2014-01-02 00:00:00

  • Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation.

    abstract::Recurrent mutations in cohesin complex proteins have been identified in pre-leukemic hematopoietic stem cells and during the early development of acute myeloid leukemia and other myeloid malignancies. Although cohesins are involved in chromosome separation and DNA damage repair, cohesin complex functions during hemato...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Mazumdar C,Shen Y,Xavy S,Zhao F,Reinisch A,Li R,Corces MR,Flynn RA,Buenrostro JD,Chan SM,Thomas D,Koenig JL,Hong WJ,Chang HY,Majeti R

    更新日期:2015-12-03 00:00:00

  • The hair follicle bulge stem cell niche resists transformation by the hedgehog pathway.

    abstract::Similarities between basal cell carcinoma (BCC) tumor cells and hair follicle keratinocytes had previously suggested that BCC originates within the hair follicle bulge stem cell niche. However, in the current Nature Cell Biology, Youssef et al. (2010) show that BCC instead originates in the interfollicular epidermis. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Ridky TW,Khavari PA

    更新日期:2010-04-02 00:00:00

  • Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells.

    abstract::Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) can be achieved by viral-mediated transduction of defined transcription factors. Moving toward the eventual goal of clinical application, it is necessary to overcome limitations such as low reprogramming efficiency and genomic alterations due to ...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Feng B,Ng JH,Heng JC,Ng HH

    更新日期:2009-04-03 00:00:00

  • A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.

    abstract::SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental pl...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yang L,Han Y,Nilsson-Payant BE,Gupta V,Wang P,Duan X,Tang X,Zhu J,Zhao Z,Jaffré F,Zhang T,Kim TW,Harschnitz O,Redmond D,Houghton S,Liu C,Naji A,Ciceri G,Guttikonda S,Bram Y,Nguyen DT,Cioffi M,Chandar V,Hoagl

    更新日期:2020-07-02 00:00:00

  • Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation.

    abstract:VIDEO ABSTRACT:Although endogenous recruitment of adult neural stem cells has been proposed as a therapeutic strategy, clinical approaches for achieving this are lacking. Here, we show that metformin, a widely used drug, promotes neurogenesis and enhances spatial memory formation. Specifically, we show that an atypical...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Wang J,Gallagher D,DeVito LM,Cancino GI,Tsui D,He L,Keller GM,Frankland PW,Kaplan DR,Miller FD

    更新日期:2012-07-06 00:00:00

  • Erosion of dosage compensation impacts human iPSC disease modeling.

    abstract::Although distinct human induced pluripotent stem cell (hiPSC) lines can display considerable epigenetic variation, it has been unclear whether such variability impacts their utility for disease modeling. Here, we show that although low-passage female hiPSCs retain the inactive X chromosome of the somatic cell they are...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Mekhoubad S,Bock C,de Boer AS,Kiskinis E,Meissner A,Eggan K

    更新日期:2012-05-04 00:00:00

  • Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity.

    abstract::Defects in brain development are believed to contribute toward the onset of neuropsychiatric disorders, but identifying specific underlying mechanisms has proven difficult. Here, we took a multifaceted approach to investigate why 15q11.2 copy number variants are prominent risk factors for schizophrenia and autism. Fir...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yoon KJ,Nguyen HN,Ursini G,Zhang F,Kim NS,Wen Z,Makri G,Nauen D,Shin JH,Park Y,Chung R,Pekle E,Zhang C,Towe M,Hussaini SM,Lee Y,Rujescu D,St Clair D,Kleinman JE,Hyde TM,Krauss G,Christian KM,Rapoport JL,Wein

    更新日期:2014-07-03 00:00:00

  • Growth signaling at the nexus of stem cell life and death.

    abstract::Stress can activate tumor-suppressive mechanisms, causing the loss of adult stem cell function with age. In this issue of Cell Stem Cell and in Nature, Castilho et al. (2009) and Harrison et al. (2009) highlight the importance of mTOR signaling in stem cell exhaustion and mammalian aging, respectively. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Wood KC,Sabatini DM

    更新日期:2009-09-04 00:00:00

  • Single-Cell Transcriptomics Meets Lineage Tracing.

    abstract::Reconstructing lineage relationships between cells within a tissue or organism is a long-standing aim in biology. Traditionally, lineage tracing has been achieved through the (genetic) labeling of a cell followed by the tracking of its offspring. Currently, lineage trajectories can also be predicted using single-cell ...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Kester L,van Oudenaarden A

    更新日期:2018-08-02 00:00:00

  • Banking human induced pluripotent stem cells: lessons learned from embryonic stem cells?

    abstract::The generation of human embryonic stem cell banking networks has ensured that well-characterized and quality controlled stem cell lines are broadly accessible to researchers worldwide. Here, we provide recommendations for engaging these established networks in efforts to build similar resources for the distribution an...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Stacey GN,Crook JM,Hei D,Ludwig T

    更新日期:2013-10-03 00:00:00

  • Young and Restless: Expansion of Donor-Origin Mutant HSCs after Transplantation.

    abstract::In a study of young adults chosen as unrelated hematopoietic stem cell donors for patients with hematological malignancies, leukemia-associated mutations were detectable in cells from 44% of donors. Donor-origin mutant clones engrafted in recipients and expanded during the first 100 days after transplant, but donor-de...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Steensma DP

    更新日期:2020-03-05 00:00:00

  • Primed for pluripotency.

    abstract::To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of pri...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Kunath T

    更新日期:2011-03-04 00:00:00

  • A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS.

    abstract::Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe a new small molecule survival screen carried out using MNs from both wild-type and mutant SOD1 mouse embryonic stem cell...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yang YM,Gupta SK,Kim KJ,Powers BE,Cerqueira A,Wainger BJ,Ngo HD,Rosowski KA,Schein PA,Ackeifi CA,Arvanites AC,Davidow LS,Woolf CJ,Rubin LL

    更新日期:2013-06-06 00:00:00

  • A Little Bit of Guidance: Mini Brains on Their Route to Adolescence.

    abstract::Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of hum...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Koch P,Ladewig J

    更新日期:2017-08-03 00:00:00

  • In epigenetic therapy, less is more.

    abstract::How DNA methylation inhibitors exert their anticancer effects in patients is not well understood. In the latest issue of Cancer Cell, Tsai et al. (2012) use low-dose drug treatment to induce persistent attenuation of tumorigenicity by targeting tumor-initiating cells. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Shen H,Laird PW

    更新日期:2012-04-06 00:00:00

  • Targeting epigenetics to speed up repair.

    abstract::In this issue of Cell Stem Cell, Palii et al. reveal that TAL1 is a master regulator of adhesion and migration networks in human endothelial progenitors and that ex vivo treatment with the histone deacetylase inhibitor TSA enables their faster vascularization after ischemic injury. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Soler E,Grosveld F

    更新日期:2014-05-01 00:00:00

  • A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.

    abstract::Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises norma...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yan HHN,Siu HC,Law S,Ho SL,Yue SSK,Tsui WY,Chan D,Chan AS,Ma S,Lam KO,Bartfeld S,Man AHY,Lee BCH,Chan ASY,Wong JWH,Cheng PSW,Chan AKW,Zhang J,Shi J,Fan X,Kwong DLW,Mak TW,Yuen ST,Clevers H,Leung SY

    更新日期:2018-12-06 00:00:00

  • Regenerative Rehabilitation: Applied Biophysics Meets Stem Cell Therapeutics.

    abstract::The emerging field of regenerative rehabilitation integrates biological and bioengineering advances in regenerative medicine with rehabilitative sciences. Here we highlight recent stem cell-based examples of the regenerative rehabilitation paradigm to promote tissue repair and regeneration, and we discuss remaining ch...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Rando TA,Ambrosio F

    更新日期:2018-03-01 00:00:00

  • Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.

    abstract::Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations clo...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yan KS,Gevaert O,Zheng GXY,Anchang B,Probert CS,Larkin KA,Davies PS,Cheng ZF,Kaddis JS,Han A,Roelf K,Calderon RI,Cynn E,Hu X,Mandleywala K,Wilhelmy J,Grimes SM,Corney DC,Boutet SC,Terry JM,Belgrader P,Ziraldo SB

    更新日期:2017-07-06 00:00:00

  • Pluripotency on Lockdown after Deletion of Three Transcription Regulators.

    abstract::Exit from the naive pluripotent state occurs through a series of changes in the gene regulatory circuitry, allowing cells to become primed for lineage commitment. In this issue of Cell Stem Cell, Kalkan et al. (2019) show that three transcription regulators are required for naive mouse embryonic stem cells (ESCs) to e...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Mitchell JA

    更新日期:2019-05-02 00:00:00

  • Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds.

    abstract::Somatic cells can be induced into pluripotent stem cells (iPSCs) with a combination of four transcription factors, Oct4/Sox2/Klf4/c-Myc or Oct4/Sox2/Nanog/LIN28. This provides an enabling platform to obtain patient-specific cells for various therapeutic and research applications. However, several problems remain for t...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Shi Y,Desponts C,Do JT,Hahm HS,Schöler HR,Ding S

    更新日期:2008-11-06 00:00:00

  • Metabolic regulation of hematopoietic stem cells in the hypoxic niche.

    abstract::Tissue homeostasis over the life of an organism relies on both self-renewal and multipotent differentiation of stem cells. Hematopoietic stem cells (HSCs) reside in a hypoxic bone marrow environment, and their metabolic status is distinct from that of their differentiated progeny. HSCs generate energy mainly via anaer...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Suda T,Takubo K,Semenza GL

    更新日期:2011-10-04 00:00:00

  • Tracing the life of the kidney tubule- re-establishing dogma and redirecting the options.

    abstract::Renal pathology suggests that tubular repair results from tubular proliferation. In contrast, recent studies propose that postnatal kidney repair may involve renal stem cells. In this issue of Cell Stem Cell, Humphreys et al. (2008) use lineage tracing to genetically assess contribution of adult nontubular cells (pote...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Little MH

    更新日期:2008-03-06 00:00:00

  • Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo.

    abstract::Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques includin...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Ramos AD,Diaz A,Nellore A,Delgado RN,Park KY,Gonzales-Roybal G,Oldham MC,Song JS,Lim DA

    更新日期:2013-05-02 00:00:00

  • Naive versus Primed: It's Now Three-Dimensional.

    abstract::We are only beginning to understand the higher-order chromatin structure of pluripotent stem cells and its relevance to cell fate. Three recent studies used different approaches to reconstruct the 3D chromatin landscape of naive and primed pluripotent cells, unveiling common features as well as differences between the...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Wei Z,Lu W

    更新日期:2016-02-04 00:00:00