Suzanne M Watt

NHS Blood and Transplant, Watford, England, United Kingdom

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Publications (122)555.37 Total impact

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    ABSTRACT: The differentiation of human pluripotent stem cells to the B-cell lymphoid lineage has important clinical applications that include in-vitro modelling of developmental lymphogenesis in health and disease. Here, we first demonstrate the capacity of human induced pluripotent stem cells (hiPSCs) to differentiate into CD144+CD73-CD43/CD235a-, cells, characterised as hemogenic endothelium, and show this population is capable of differentiating to CD10+CD19+ B lymphocytes. We also demonstrate that B lymphocytes generated from hiPSCs are able to undergo full VDJ rearrangement and express surface IgM (sIgM+), thus representating an immature B-cell subset. Efficiency of sIgM expression on the iPS-derived B lymphocytes (c. 5% of CD19+ cells) was comparable with B lymphocytes generated from human umbilical cord blood hematopoietic progenitor cells. Importantly, when assessed by global transcriptional profiling, hiPSC-derived B-cells show a very high level of similarity when compared to their umbilical cord blood derived counterparts, such that from over 47,000 different transcripts, only 45 were significantly different (with a criteria adjusted P value P˂0.05, log FC ˃1.0 or 2.8 fold). This represents a unique in-vitro model to delineate critical events during lymphogeneisis in development and lymphoid diseases such as acute lymphocytic leukemia.
    Stem Cells and Development 12/2014; · 4.20 Impact Factor
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    ABSTRACT: Human cord blood (CB) hematopoietic stem (HSC) cell transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet biased murine HSC subset, maintained by thrombopoietin (TPO) which has enhanced capacity for short and long term platelet reconstitution, can self-renew, and can give rise to myeloid and lymphoid biased HSCs. In previous studies, we have shown that transplantation of human CB CD34+ cells pre-cultured in TPO as a single graft accelerates early platelet recovery as well as yielding long term repopulation in immune deficient mice. Here, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34+ cells have a competitive advantage or disadvantage over untreated human CB CD34+ cells in terms of i) short and longer term platelet recovery and ii) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34+ cells. Notably, this was followed by a dominant contribution to platelet production via the untreated CD34+ cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long term chimerism in vivo.
    Stem Cells and Development 08/2014; · 4.20 Impact Factor
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    ABSTRACT: Proangiogenic factors, VEGF and FGF-2, prime endothelial cells to respond to 'hematopoietic' chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Co-culture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the 'hematopoietic' chemokine CXCL12 and its CXCR4 receptor by day 3 of co-culture. Chronic exposure to the CXCR4 antagonist, AMD-3100, in this vasculo/angio-genesis assay, significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14 day co-cultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by live cell imaging. Secondly, at earlier stages of co-cultures, we observed that AMD3100 significantly inhibited the integration of exogenous ECFC-derived cells into established, but immature, vascular networks. Comparative proteome profiler array analyses of ECFC-derived cells treated with AMD3100 identified changes in expression of potential candidate molecules involved in adhesion and/or migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC-derived cell integration into these extant vascular networks. Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks.
    Stem Cells and Development 06/2014; · 4.20 Impact Factor
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    ABSTRACT: Human induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of origin or method of reprogramming, hiPSCs can be differentiated on OP9 stroma towards a multi-lineage haemo-endothelial progenitor that can contribute to CD144+ endothelium, CD235a+ erythrocytes (myeloid lineage) and CD19+ B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hiPSC-derived erythroblasts express alpha globin as previously described, and that a sub-population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub-fraction of HbF positive erythroblasts co-expressed HbA in a highly heterogeneous manner, but analogous to cord blood-derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum-free approach was employed to isolate a CD31+ CD45+ erythro-myeloid progenitor. These findings demonstrate that hiPSCs may represent a useful alternative to standard sources of erythrocytes (RBCs) for future applications in transfusion medicine.
    British Journal of Haematology 05/2014; · 4.94 Impact Factor
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    ABSTRACT: Cryopreserved umbilical cord blood (CB) is increasingly used as a cell source to reconstitute marrow in hematopoietic stem cell transplant patients. Delays in cryopreservation may adversely affect cell viability, thereby reducing their potential for engraftment after transplantation. The impact of delayed cryopreservation for up to 3 days on the viability of both CD45+ and CD34+ cell populations in 28 CB donations with volumes of 58.40 ± 15.4 mL (range, 39.4-107.4 mL) was investigated to establish whether precryopreservation storage time could be extended from our current time of 24 to 48 hours in line with other CB banks. Viability was assessed on 3 consecutive days, both before and after cryopreservation, by flow cytometry using 7-aminoactinomycin D (7-AAD) and annexin V methods. The results using 7-AAD and annexin V indicated the viability of CD34+ cells before cryopreservation remained high (>92.33 ± 4.11%) over 3 days, whereas the viability of CD45+ cells decreased from 86.36 ± 4.97% to 66.24 ± 7.78% (p < 0.0001) by Day 3. Storage time significantly affected the viability of CD34+ cells after cryopreservation. Using 7-AAD, the mean CD34+ cell viability decreased by approximately 5% per extra day in storage from 84.30 ± 6.27% on Day 1 to 79.01 ± 7.44% (p < 0.0057) on Day 2 and to 73.95 ± 7.54% (p < 0.0001) on Day 3. With annexin V staining CD34+ cell viability fell by approximately 7% per extra day in storage from 77.17 ± 8.47% on Day 1 to 69.56 ± 13.30% (p < 0.0194) on Day 2 and to 62.89 ± 15.22% (p < 0.0002) on Day 3. This study demonstrates that extended precryopreservation storage adversely affects viability and should be avoided.
    Transfusion 11/2013; · 3.57 Impact Factor
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    ABSTRACT: Adoptive cell therapy employing gene-modified T-cells expressing chimeric antigen receptors (CARs) has shown promising preclinical activity in a range of model systems and is now being tested in the clinical setting. The manufacture of CAR T-cells requires compliance with national and European regulations for the production of medicinal products. We established such a compliant process to produce T-cells armed with a first-generation CAR specific for carcinoembryonic antigen (CEA). CAR T-cells were successfully generated for 14 patients with advanced CEA(+) malignancy. Of note, in the majority of patients, the defined procedure generated predominantly CD4(+) CAR T-cells with the general T-cell population bearing an effector-memory phenotype and high in vitro effector function. Thus, improving the process to generate less-differentiated T-cells would be more desirable in the future for effective adoptive gene-modified T-cell therapy. However, these results confirm that CAR T-cells can be generated in a manner compliant with regulations governing medicinal products in the European Union.
    Cancer Immunology and Immunotherapy 11/2013; 63(2). · 3.64 Impact Factor
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    ABSTRACT: The treatment of full thickness skin loss, which can be extensive in the case of large burns, continues to represent a challenging clinical entity. This is due to an on-going inability to produce a suitable tissue engineered substrate that can satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both aesthetic and functional demands. The current gold standard treatment of autologous skin grafting is inadequate because of poor textural durability, scarring and associated contracture, and because of a paucity of donor sites in larger burns. Tissue engineering has seen exponential growth in recent years with a number of 'off-the-shelf' dermal and epidermal substitutes now available. Each has its own limitations. In this review, we examine normal wound repair in relation to stem/progenitor cells that are intimately involved in this process within the dermal niche. Endothelial precursors, in particular, are examined closely and their phenotype, morphology and enrichment from multiple sources are described in an attempt to provide some clarity regarding the controversy surrounding their classification and role in vasculogenesis. We also review the role of the next generation of cellularized scaffolds and smart biomaterials that attempt to improve the revascularisation of artificial grafts, the rate of wound healing and the final cosmetic and functional outcome. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 10/2013; · 4.43 Impact Factor
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    ABSTRACT: Background Blood vessel formation is fundamental to development, while its dysregulation can contribute to serious disease. Expectations are that hundreds of millions of individuals will benefit from therapeutic developments in vascular biology. MSCs are central to the three main vascular repair mechanisms.Sources of dataKey recent published literature and ClinicalTrials.gov.Areas of agreementMSCs are heterogeneous, containing multi-lineage stem and partly differentiated progenitor cells, and are easily expandable ex vivo. There is no single marker defining native MSCs in vivo. Their phenotype is strongly determined by their specific microenvironment. Bone marrow MSCs have skeletal stem cell properties. Having a perivascular/vascular location, they contribute to vascular formation and function and might be harnessed to regenerate a blood supply to injured tissues.Areas of controversyThese include MSC origin, phenotype and location in vivo and their ability to differentiate into functional cardiomyocytes and endothelial cells or act as vascular stem cells. In addition their efficacy, safety and potency in clinical trials in relation to cell source, dose, delivery route, passage and timing of administration, but probably even more on the local preconditioning and the mechanisms by which they exert their effects.Growing pointsUnderstanding the origin and the regenerative environment of MSCs, and manipulating their homing properties, proliferative ability and functionality through drug discovery and reprogramming strategies are important for their efficacy in vascular repair for regenerative medicine therapies and tissue engineering approaches.Areas timely for developing researchCharacterization of MSCs' in vivo origins and biological properties in relation to their localization within tissue niches, reprogramming strategies and newer imaging/bioengineering approaches.
    British Medical Bulletin 10/2013; · 4.36 Impact Factor
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    Emma E Pepperell, Suzanne M Watt
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    ABSTRACT: Efficient homing/mobilization of human hematopoietic stem/progenitor cells to/from bone marrow niches enhances their therapeutic efficacy. Additionally, homing is dependent on cell source and may be modulated by prior ex vivo cell expansion. Here, we describe a novel application of a 3-dimensional time-lapse method for assessing trafficking of individual human cord blood CD133(+) hematopoietic stem/progenitor cells in vitro, using the key chemokine CXCL12 as a paradigm. This new methodology allows distinction between chemotactic responses (displacement of center of mass and the forward migration index of the cells), and chemokinetic responses such as total cell path traveled in any direction (accumulated distance) and cell velocity in a 3-dimensional matrix. Other key advantages of this novel assay over existing assays include the ability to assess individual cell migration over times comparable to in vivo homing and rapid mobilization assays (18-24h) and to directly compare the strength or response of individual hematopoietic progenitor cells to different or competing stimuli and small molecule inhibitors in a single assay prior to analyses in vivo. Importantly, using this method, our results demonstrate definitively that CXCL12 regulates the chemotactic responses of human cord blood CD133(+) cells, but not their random migration or chemokinesis.
    Stem Cell Research 04/2013; 11(2):707-720. · 4.47 Impact Factor
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    ABSTRACT: Previous attempts to identify neuroprotective targets by studying the ischemic cascade and devising ways to suppress it have failed to translate to efficacious therapies for acute ischemic stroke. We hypothesized that studying the molecular determinants of endogenous neuroprotection in two well-established paradigms, the resistance of CA3 hippocampal neurons to global ischemia and the tolerance conferred by ischemic preconditioning (IPC), would reveal new neuroprotective targets. We found that the product of the tuberous sclerosis complex 1 gene (TSC1), hamartin, is selectively induced by ischemia in hippocampal CA3 neurons. In CA1 neurons, hamartin was unaffected by ischemia but was upregulated by IPC preceding ischemia, which protects the otherwise vulnerable CA1 cells. Suppression of hamartin expression with TSC1 shRNA viral vectors both in vitro and in vivo increased the vulnerability of neurons to cell death following oxygen glucose deprivation (OGD) and ischemia. In vivo, suppression of TSC1 expression increased locomotor activity and decreased habituation in a hippocampal-dependent task. Overexpression of hamartin increased resistance to OGD by inducing productive autophagy through an mTORC1-dependent mechanism.
    Nature medicine 02/2013; 19(3):351-7. · 28.05 Impact Factor
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    ABSTRACT: Human amniotic fluid obtained at amniocentesis, when cultured, generates at least two morphologically distinct mesenchymal stem/stromal cell (MSC) subsets. Of these, the spindle shaped amniotic fluid MSCs (SS-AF-MSCs) contain multipotent cells with enhanced adipogenic, osteogenic and chondrogenic capacity. Here, we demonstrate, for the first time, the capacity of these SS-AF-MSCs to support neovascularization by umbilical cord blood (UCB) endothelial colony forming cell (ECFC) derived cells in both in vitro and in vivo models. Interestingly, although the kinetics of vascular tubule formation in vitro were similar when the supporting SS-AF-MSCs were compared with the best vasculogenic supportive batches of bone marrow MSCs (BMSCs) or human dermal fibroblasts (hDFs), SS-AF-MSCs supported vascular tubule formation in vivo more effectively than BMSCs. In NOD/SCID mice, the human vessels inosculated with murine vessels demonstrating their functionality. Proteome profiler array analyses revealed both common and distinct secretion profiles of angiogenic factors by the SS-AF-MSCs as opposed to the hDFs and BMSCs. Thus, SS-AF-MSCs, which are considered to be less mature developmentally than adult BMSCs, and intermediate between adult and embryonic stem cells in their potentiality, have the additional and very interesting potential of supporting increased neovascularisation, further enhancing their promise as vehicles for tissue repair and regeneration.
    PLoS ONE 01/2013; 8(1):e54747. · 3.53 Impact Factor
  • Vox Sanguinis 01/2013; 104(1):67-91. · 3.30 Impact Factor
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    ABSTRACT: To investigate the effects of age and disease on endogenous cardiac progenitor cells, we obtained right atrial and left ventricular epicardial biopsies from patients (n = 22) with chronic ischaemic heart disease and measured doubling time and surface marker expression in explant- and cardiosphere-derived cells (EDCs, CDCs). EDCs could be expanded from all atrial biopsy samples, but sufficient cells for cardiosphere culture were obtained from only 8 of 22 ventricular biopsies. EDCs from both atrium and ventricle contained a higher proportion of c-kit+ cells than CDCs, which contained few such cells. There was wide variation in expression of CD90 (atrial CDCs 5-92 % CD90+; ventricular CDCs 11-89 % CD90+), with atrial CDCs cultured from diabetic patients (n = 4) containing 1.6-fold more CD90+ cells than those from non-diabetic patients (n = 18). No effect of age or other co-morbidities was detected. Thus, CDCs from atrial biopsies may vary in their therapeutic potential.
    Journal of Cardiovascular Translational Research 07/2012; 5(5):678-87. · 3.06 Impact Factor
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    ABSTRACT: To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005-2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 10(8) cells and to patients with more severe heart dysfunction. Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials.
    PLoS ONE 05/2012; 7(5):e37373. · 3.53 Impact Factor
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    ABSTRACT: Forming a microcirculation is critical for vascularisation of artificial skin substitutes. One strategy to improve speed of grafting is to pre-form microvascular networks in the substitute before applying to a wound. For clinical application, this requires sufficient functional endothelial cell numbers. In vitro endothelial colony forming cells (ECFCs) derived cells were expanded from cord and adult blood donations and co-cultured with human dermal fibroblasts or bone marrow mesenchymal stem/stromal cells to form microvascular networks in the presence or absence of dermal substitutes which are in clinical use. The number of endothelial cells generated ranged from 1.03×10(9) to 2.18×10(11) from 10 adult blood donations and 1×10(12) to 1.76×10(13) from 6 cord blood units after 50 days in culture. Two adult donations failed to generate ECFCs. Both cord and adult blood cells formed 2D microvascular networks in vitro, although there was a significant difference in the functional capacity of adult and cord blood ECFCs. While co-culture of the latter within dermal substitutes Matriderm or Integra demonstrated the formation of 3D microvascular networks penetrating 100μm, enhanced expansion, while maintaining functional capacity, of adult blood cells is required for fully pre-vascularising the clinical grade acellular dermal substitutes used here prior to applying these to burns.
    Burns: journal of the International Society for Burn Injuries 02/2012; 38(5):691-701. · 1.95 Impact Factor
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    ABSTRACT: The bone marrow contains specific microenvironmental stem cell niches that maintain haemopoiesis. CXCL12-expressing mesenchymal stromal cells are closely associated with the bone marrow sinusoidal endothelia, forming key elements of the haemopoietic stem cell niche, yet their ability to regulate endothelial function is not clearly defined. Given that the murine nestin(+) cell line, MS-5, provides a clonal surrogate bone marrow stromal niche capable of regulating both murine and human primitive haemopoietic stem/progenitor cell (HSC/HPC) fate in vitro, we hypothesized that MS-5 cells might also support new blood vessel formation and function. Here, for the first time, we demonstrate that this is indeed the case. Using proteome arrays, we identified HSC/HPC active angiogenic factors that are preferentially secreted by haemopoietic supportive nestin(+) MS-5 cells, including CXCL12 (SDF-1), NOV (CCN3), HGF, Angiopoietin-1 and CCL2 (MCP-1). Concentrating on CXCL12, we confirmed its presence in MS-5 conditioned media and demonstrated that its antagonist in receptor binding, AMD-3100, which mobilizes HSC/HPCs and endothelial progenitors from bone marrow, could significantly reduce MS-5 mediated human vasculogenesis in vitro, principally by regulating human endothelial cell migration. Thus, the clonal nestin(+) MS-5 murine bone marrow stromal cell line not only promotes human haemopoiesis but also induces human vasculogenesis, with CXCL12 playing important roles in both processes.
    British Journal of Haematology 02/2012; 157(3):299-311. · 4.94 Impact Factor
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    ABSTRACT: Stem cell therapy offers a promising approach to the regeneration of damaged vascular and cardiac tissue after acute myocardial infarction (AMI). This has resulted in multiple randomised controlled trials (RCTs) worldwide. To critically evaluate evidence from RCTs on the effectiveness of adult bone marrow-derived stem cells (BMSC) to treat acute myocardial infarction (AMI). This Cochrane review is an update of a previous one (published in 2008). MEDLINE (1950 to January 2011), EMBASE (1974 to January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), CINAHL (1982 to January 2011) and the Transfusion Evidence Library (1980 to January 2011) were searched. In addition, several international and ongoing trial databases were searched and handsearching of relevant conference proceedings undertaken to January 2011. RCTs comparing autologous stem/progenitor cells with no autologous stem/progenitor cells in patients diagnosed with AMI were eligible. Two authors independently screened all references, assessed trial quality and extracted data. Meta-analyses using a random-effects model were conducted and heterogeneity was explored for the primary outcome using sub-group analyses. Thirty-three RCTs (1765 participants) were eligible for inclusion. Stem/progenitor cell treatment was not associated with statistically significant changes in the incidence of mortality (RR 0.70, 95% CI 0.40 to 1.21) or morbidity (the latter measured by re-infarction, hospital re-admission, restenosis and target vessel revascularisation). A considerably high degree of heterogeneity has been observed among the included trials. In short-term follow up, stem cell treatment was observed to improve left ventricular ejection fraction (LVEF) significantly (WMD 2.87, 95% CI 2.00 to 3.73). This improvement in LVEF was maintained over long-term follow up of 12 to 61 months (WMD 3.75, 95% CI 2.57 to 4.93). With certain measurements and at certain times, stem cell treatment was observed to reduce left ventricular end systolic and end diastolic volumes (LVESV & LVEDV) and infarct size significantly in long-term follow up. There was a positive correlation between mononuclear cell dose infused and the effect on LVEF measured by magnetic resonance imaging. A correlation between timing of stem cell treatment and effect on LVEF measured by left ventricular angiography was also observed. Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.
    Cochrane database of systematic reviews (Online) 01/2012; 2:CD006536. · 5.94 Impact Factor
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    ABSTRACT: Induced pluripotent stem (iPS) cells are being used increasingly to complement their embryonic counterparts to understand and develop the therapeutic potential of pluripotent cells. Our objectives were to identify an efficient cardiac differentiation protocol for human iPS cells as monolayers, and demonstrate that the resulting cardiac progenitors could provide a therapeutic benefit in a rodent model of myocardial infarction. Herein, we describe a 14-day protocol for efficient cardiac differentiation of human iPS cells as a monolayer, which routinely yielded a mixed population in which over 50% were cardiomyocytes, endothelium, or smooth muscle cells. When differentiating, cardiac progenitors from day 6 of this protocol were injected into the peri-infarct region of the rat heart; after coronary artery ligation and reperfusion, we were able to show that human iPS cell-derived cardiac progenitor cells engrafted, differentiated into cardiomyocytes and smooth muscle, and persisted for at least 10 weeks postinfarct. Hearts injected with iPS-derived cells showed a nonsignificant trend toward protection from decline in function after myocardial infarction, as assessed by magnetic resonance imaging at 10 weeks, such that the ejection fraction at 10 weeks in iPS treated hearts was 62%±4%, compared to that of control infarcted hearts at 45%±9% (P<0.2). In conclusion, we demonstrated efficient cardiac differentiation of human iPS cells that gave rise to progenitors that were retained within the infarcted rat heart, and reduced remodeling of the heart after ischemic damage.
    Stem cells and development 12/2011; 21(6):977-86. · 4.15 Impact Factor

Publication Stats

4k Citations
555.37 Total Impact Points

Institutions

  • 2006–2013
    • NHS Blood and Transplant
      Watford, England, United Kingdom
  • 1995–2013
    • Oxford University Hospitals NHS Trust
      • • Department of Haematology
      • • Department of Paediatrics
      Oxford, England, United Kingdom
  • 1999–2012
    • University of Oxford
      • • Nuffield Division of Clinical Laboratory Sciences
      • • Molecular Haematology Unit
      Oxford, ENG, United Kingdom
  • 2009
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom
  • 2008
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2007
    • Jeevan Blood and Stem Cell Bank
      Chennai, Tamil Nādu, India
  • 1991
    • Cancer Research UK
      Londinium, England, United Kingdom
  • 1983
    • University of Cambridge
      • Department of Pathology
      Cambridge, England, United Kingdom
  • 1977–1981
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1979
    • Walter And Eliza Hall Institute For Medical Research
      Melbourne, Victoria, Australia