In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors
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ABSTRACT:
PROVIDER: PRJNA392876 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the SubSeries listed below and contains: bulk RNA-seq of two time series of a xeno-free human cardiomyocyte differentiation protocol starting from HS1001 and H1 hECSs until day 94 cardiomyocytes, single cell sequencing of cardiovascular progenitors (H1 and HS1001-derived cardiovascular progenitors at day 9 and 11) and bulk RNA-Seq of H1 hECSs that have been transferred to a LN-221 matrix. Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.
2019-03-21 | GSE100725 | GEO
Project description:Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.
2019-04-26 | GSE101132 | GEO
Project description:Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.
2019-04-26 | GSE100722 | GEO
Project description:Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.
2019-04-26 | GSE101076 | GEO
Project description:Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.
2019-03-20 | GSE127955 | GEO
Project description:In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [HS1001 differentiation protocol]
| PRJNA392969 | ENA
Project description:In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [H1 differentiation protocol]
| PRJNA393784 | ENA
Project description:Stem cell-derived products could replace damaged heart muscle in regenerative cardiology. Here, human embryonic stem cells (hESCs) were differentiated on laminin 521+221 to cardiovascular progenitors (CVPs). The CVPs were transplanted into the infarcted region of 10 pigs and maintained for 4- and 12- weeks. Immunohistology analyses revealed in vivo engraftment and maturation of the CVPs into cardiomyocytes (CMs). Furthermore, heart function was analyzed by magnetic resonance imaging (MRI). We observed significant improvement in the left ventricular ejection fraction (DLVEF: 21.9 ± 1.6 %, at 12-weeks), ventricular wall thickness and wall motion, as well as a reduction in infarction size after CVP transplantation as compared to control pigs (p-value < 0.05). There are temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and one pig had persistent VT. On the other hand, the remaining 5 pigs remained in normal sinus rhythm. Importantly, all pigs survived without any VT-related death, suggesting the potential for developing CVPs towards applications in regenerative cardiology.
2023-01-31 | GSE204881 | GEO
Project description:In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors [LN-521 or LN-521+LN-221]
| PRJNA393685 | ENA
Project description:Comparison of laminin binding and laminin non-binding germ cells Keywords: other
2004-03-16 | GSE829 | GEO