Brachyury engineers cardiac repair competent stem cells.

Abstract:

:To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of the current stem cell enhancement protocol. To this end, the microencapsulated-modified-mRNA (M3 RNA) technique was here applied to introduce early cardiogenic genes into human adipose-derived mesenchymal stem cells (AMSCs). A single mesodermal transcription factor, Brachyury, was sufficient to trigger high expression of cardiopoietic markers, Nkx2.5 and Mef2c. Engineered cardiopoietic stem cells (eCP) featured a transcriptome profile distinct from pre-engineered AMSCs. In vitro, eCP demonstrated protective antioxidant capacity with enhanced superoxide dismutase expression and activity; a vasculogenic secretome driving angiogenic tube formation; and macrophage polarizing immunomodulatory properties. In vivo, in a murine model of myocardial infarction, intramyocardial delivery of eCP (600 000 cells per heart) improved cardiac performance and protected against decompensated heart failure. Thus, heart repair competent stem cells, armed with antioxidant, vasculogenic, and immunomodulatory traits, are here engineered through a protein-independent single gene manipulation, expanding the available regenerative toolkit.

journal_name

Stem Cells Transl Med

authors

Li M,Yamada S,Shi A,Singh RD,Rolland TJ,Jeon R,Lopez N,Shelerud L,Terzic A,Behfar A

doi

10.1002/sctm.20-0193

subject

Has Abstract

pub_date

2020-10-24 00:00:00

eissn

2157-6564

issn

2157-6580

pub_type

杂志文章
  • Reliable generation of induced pluripotent stem cells from human lymphoblastoid cell lines.

    abstract::Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for many applications, including disease modeling to elucidate mechanisms involved in disease pathogenesis, drug screening, and ultimately regenerative medicine therapies. A frequently used starting source of cells for reprogramming has been de...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0121

    authors: Barrett R,Ornelas L,Yeager N,Mandefro B,Sahabian A,Lenaeus L,Targan SR,Svendsen CN,Sareen D

    更新日期:2014-12-01 00:00:00

  • Proceedings: human leukocyte antigen haplo-homozygous induced pluripotent stem cell haplobank modeled after the california population: evaluating matching in a multiethnic and admixed population.

    abstract::The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0052

    authors: Pappas DJ,Gourraud PA,Le Gall C,Laurent J,Trounson A,DeWitt N,Talib S

    更新日期:2015-05-01 00:00:00

  • Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

    abstract::Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical c...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0472

    authors: Lanzoni G,Linetsky E,Correa D,Messinger Cayetano S,Alvarez RA,Kouroupis D,Alvarez Gil A,Poggioli R,Ruiz P,Marttos AC,Hirani K,Bell CA,Kusack H,Rafkin L,Baidal D,Pastewski A,Gawri K,Leñero C,Mantero AMA,Metalonis SW

    更新日期:2021-01-05 00:00:00

  • Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities.

    abstract::Long-term lentiviral transduction of human mesenchymal stem cells (hMSCs) greatly enhances the usefulness of these cells. However, such transduction currently requires the use of polybrene, which severely inhibits hMSC proliferation. In contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0086

    authors: Lin P,Lin Y,Lennon DP,Correa D,Schluchter M,Caplan AI

    更新日期:2012-12-01 00:00:00

  • Mesenchymal Stromal Cell-Seeded Biomimetic Scaffolds as a Factory of Soluble RANKL in Rankl-Deficient Osteopetrosis.

    abstract::Biomimetic scaffolds are extremely versatile in terms of chemical composition and physical properties, which can be defined to accomplish specific applications. One property that can be added is the production/release of bioactive soluble factors, either directly from the biomaterial, or from cells embedded within the...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0085

    authors: Menale C,Campodoni E,Palagano E,Mantero S,Erreni M,Inforzato A,Fontana E,Schena F,Van't Hof R,Sandri M,Tampieri A,Villa A,Sobacchi C

    更新日期:2019-01-01 00:00:00

  • Distinct mobilization of circulating CD271+ mesenchymal progenitors from hematopoietic progenitors during aging and after myocardial infarction.

    abstract::The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271(+) MSCs in human periphe...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2011-0051

    authors: Iso Y,Yamaya S,Sato T,Poole CN,Isoyama K,Mimura M,Koba S,Kobayashi Y,Takeyama Y,Spees JL,Suzuki H

    更新日期:2012-06-01 00:00:00

  • Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease.

    abstract::An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical a...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2015-0101

    authors: Golpanian S,Schulman IH,Ebert RF,Heldman AW,DiFede DL,Yang PC,Wu JC,Bolli R,Perin EC,Moyé L,Simari RD,Wolf A,Hare JM,Cardiovascular Cell Therapy Research Network.

    更新日期:2016-02-01 00:00:00

  • Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development.

    abstract::Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0200

    authors: Xia Q,Zhu S,Wu Y,Wang J,Cai Y,Chen P,Li J,Heng BC,Ouyang HW,Lu P

    更新日期:2015-05-01 00:00:00

  • Specimen collection for induced pluripotent stem cell research: harmonizing the approach to informed consent.

    abstract::Induced pluripotent stem cells (iPSCs) have elicited excitement in both the scientific and ethics communities for their potential to advance basic and translational research. They have been hailed as an alternative to derivation from embryos that provides a virtually unlimited source of pluripotent stem cells for rese...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0029

    authors: Lowenthal J,Lipnick S,Rao M,Hull SC

    更新日期:2012-05-01 00:00:00

  • Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis.

    abstract::The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0045

    authors: Redondo J,Sarkar P,Kemp K,Heesom KJ,Wilkins A,Scolding NJ,Rice CM

    更新日期:2018-10-01 00:00:00

  • Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture.

    abstract::Xenogeneic-free media are required for translating advanced therapeutic medicinal products to the clinics. In addition, process efficiency is crucial for ensuring cost efficiency, especially when considering large-scale production of mesenchymal stem cells (MSCs). Human platelet lysate (HPL) has been increasingly adop...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0216

    authors: Gupta P,Hall GN,Geris L,Luyten FP,Papantoniou I

    更新日期:2019-08-01 00:00:00

  • Concise Review: Exploiting Unique Biological Features of Leukemia Stem Cells for Therapeutic Benefit.

    abstract::Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.18-0247

    authors: Zhang H,Li S

    更新日期:2019-08-01 00:00:00

  • Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    abstract::Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persis...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0022

    authors: Santana MM,Chung KF,Vukicevic V,Rosmaninho-Salgado J,Kanczkowski W,Cortez V,Hackmann K,Bastos CA,Mota A,Schrock E,Bornstein SR,Cavadas C,Ehrhart-Bornstein M

    更新日期:2012-11-01 00:00:00

  • Prospect of stem cells conditioned medium (secretome) in ligament and tendon healing: A systematic review.

    abstract:BACKGROUND:Tendon or ligament tears can decrease patients' quality of life. Many therapeutic interventions are available to treat such injuries. Mesenchymal stem cells (MSCs) have been shown to be effective in treating tendon or ligament tears; however, the use of stem cell-conditioned medium (CM) requires further inve...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.19-0388

    authors: Rhatomy S,Prasetyo TE,Setyawan R,Soekarno NR,Romaniyanto F,Sedjati AP,Sumarwoto T,Utomo DN,Suroto H,Mahyudin F,Prakoeswa CRS

    更新日期:2020-08-01 00:00:00

  • Sp1 transcription factor interaction with accumulated prelamin a impairs adipose lineage differentiation in human mesenchymal stem cells: essential role of sp1 in the integrity of lipid vesicles.

    abstract::Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2011-0010

    authors: Ruiz de Eguino G,Infante A,Schlangen K,Aransay AM,Fullaondo A,Soriano M,García-Verdugo JM,Martín AG,Rodríguez CI

    更新日期:2012-04-01 00:00:00

  • Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.

    abstract:UNLABELLED:Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days durin...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0155

    authors: Mandò C,Razini P,Novielli C,Anelli GM,Belicchi M,Erratico S,Banfi S,Meregalli M,Tavelli A,Baccarin M,Rolfo A,Motta S,Torrente Y,Cetin I

    更新日期:2016-04-01 00:00:00

  • CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.

    abstract::Techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. However, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achi...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0019

    authors: Ostrominski JW,Yada RC,Sato N,Klein M,Blinova K,Patel D,Valadez R,Palisoc M,Pittaluga S,Peng KW,San H,Lin Y,Basuli F,Zhang X,Swenson RE,Haigney M,Choyke PL,Zou J,Boehm M,Hong SG,Dunbar CE

    更新日期:2020-10-01 00:00:00

  • Stem-Cell Therapy for Esophageal Anastomotic Leakage by Autografting Stromal Cells in Fibrin Scaffold.

    abstract::Esophageal anastomotic leakage (EAL) is a devastating complication for esophagectomy but the available therapies are unsatisfactory. Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffold (FS), we evaluated the efficacy of a stem-cell therapy for EAL by engrafting a...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0137

    authors: Xue X,Yan Y,Ma Y,Yuan Y,Li C,Lang X,Xu Z,Chen H,Zhang H

    更新日期:2019-06-01 00:00:00

  • A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research and Regenerative Medicine Between the Public and the Scientific Community.

    abstract::Owing to the rapid progress in stem cell research (SCR) and regenerative medicine (RM), society's expectation and interest in these fields are increasing. For effective communication on issues concerning SCR and RM, surveys for understanding the interests of stakeholders is essential. For this purpose, we conducted a ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0184

    authors: Shineha R,Inoue Y,Ikka T,Kishimoto A,Yashiro Y

    更新日期:2018-02-01 00:00:00

  • Cartilage repair using human embryonic stem cell-derived chondroprogenitors.

    abstract::In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and va...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0101

    authors: Cheng A,Kapacee Z,Peng J,Lu S,Lucas RJ,Hardingham TE,Kimber SJ

    更新日期:2014-11-01 00:00:00

  • Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

    abstract::For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of t...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0024

    authors: Badja C,Maleeva G,El-Yazidi C,Barruet E,Lasserre M,Tropel P,Binetruy B,Bregestovski P,Magdinier F

    更新日期:2014-12-01 00:00:00

  • Hierarchy of breast cancer cells: key to reverse dormancy for therapeutic intervention.

    abstract::An understanding of how cancer cells adapt dormancy would allow for targeted treatment. The current literature suggests that the cancer stem cells might be the major cells with the ability to become quiescent and to resist current drug treatment. The properties of cancer stem cells and healthy stem cells are functiona...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2014-0013

    authors: Bliss SA,Greco SJ,Rameshwar P

    更新日期:2014-07-01 00:00:00

  • Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    abstract::Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expan...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2013-0071

    authors: Flores-Guzmán P,Fernández-Sánchez V,Mayani H

    更新日期:2013-11-01 00:00:00

  • Erythropoietin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in an Aneurysm Neck After Coil Embolization by Modulating Vascular Endothelial Growth Factor.

    abstract:UNLABELLED:: This study explored a new approach to enhance aneurysm (AN) neck endothelialization via erythropoietin (EPO)-induced endothelial progenitor cell (EPC) stimulation. Results suggest that EPO enhanced the endothelialization of a coiled embolization AN neck by stimulating EPCs via vascular endothelial growth f...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0264

    authors: Liu P,Zhou Y,An Q,Song Y,Chen X,Yang GY,Zhu W

    更新日期:2016-09-01 00:00:00

  • Platelet-rich plasma greatly potentiates insulin-induced adipogenic differentiation of human adipose-derived stem cells through a serine/threonine kinase Akt-dependent mechanism and promotes clinical fat graft maintenance.

    abstract::The potential plasticity and therapeutic utility in tissue regeneration of human adipose-derived stem cells (ASCs) isolated from adult adipose tissue have recently been highlighted. The use of autologous platelet-rich plasma (PRP) represents an alternative strategy in regenerative medicine for the local release of mul...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.5966/sctm.2011-0052

    authors: Cervelli V,Scioli MG,Gentile P,Doldo E,Bonanno E,Spagnoli LG,Orlandi A

    更新日期:2012-03-01 00:00:00

  • Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial.

    abstract::We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogene...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1002/sctm.16-0227

    authors: Pang Y,Xiao HW,Zhang H,Liu ZH,Li L,Gao Y,Li HB,Jiang ZJ,Tan H,Lin JR,Du X,Weng JY,Nie DN,Lin DJ,Zhang XZ,Liu QF,Xu DR,Chen HJ,Ge XH,Wang XY,Xiao Y

    更新日期:2017-07-01 00:00:00

  • Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet β-cell Function in Humans.

    abstract::Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet β cells, but these challenges have proven...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0078

    authors: Zhao Y,Jiang Z,Delgado E,Li H,Zhou H,Hu W,Perez-Basterrechea M,Janostakova A,Tan Q,Wang J,Mao M,Yin Z,Zhang Y,Li Y,Li Q,Zhou J,Li Y,Martinez Revuelta E,Maria García-Gala J,Wang H,Perez-Lopez S,Alvarez-Viejo M,

    更新日期:2017-08-01 00:00:00

  • Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon.

    abstract::Stem cells have been widely used in tendon tissue engineering. The lack of refined and controlled differentiation strategy hampers the tendon repair and regeneration. This study aimed to find new effective differentiation factors for stepwise tenogenic differentiation. By microarray screening, the transcript factor Fo...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.15-0146

    authors: Chen J,Zhang E,Zhang W,Liu Z,Lu P,Zhu T,Yin Z,Backman LJ,Liu H,Chen X,Ouyang H

    更新日期:2017-11-01 00:00:00

  • In Vivo Formation of Stable Hyaline Cartilage by Naïve Human Bone Marrow Stromal Cells with Modified Fibrin Microbeads.

    abstract::Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal and surgical approaches are often ineffective, and the supply of autologous chondrocytes for tissue engineering is very limited. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) h...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0129

    authors: Kuznetsov SA,Hailu-Lazmi A,Cherman N,de Castro LF,Robey PG,Gorodetsky R

    更新日期:2019-06-01 00:00:00

  • Convergence of Cell Pharmacology and Drug Delivery.

    abstract::Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting prin...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.19-0019

    authors: Aijaz A,Vaninov N,Allen A,Barcia RN,Parekkadan B

    更新日期:2019-09-01 00:00:00