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A Comparison of the Efficacy of Transplantation of Bone Marrow Derived Mesenchymal Stem Cells and Unrestricted Somatic Stem Cells on Outcome After Acute Myocardial Infarction

ABSTRACT: Unrestricted Somatic Stem Cells (USSC) are a cell population derived from umbilical cord blood. They have been shown to have greater plasticity than mesenchymal stem cells, and are being investigated as a therapeutic option for many disease states, including cardiovascular disease.

In this study, we aimed to evaluate the efficacy of USSC on treating acute myocardial infarction (MI). We compared the effectiveness of USSC to the more widely studied bone marrow derived mesenchymal stem cell. Finally, we investigated whether pre-conditioning USSC prior to administration enhances their effectiveness. We determined effectiveness primarily using cardiac ultrasound, and supported these findings with histological analyses.

We observed that pre-conditioned (guided) USSC had the most significant beneficial effect on cardiac function. (Pre-conditioned cells were grown in serum-free F12 media was supplemented with 50ng/ml Basic Fibroblast Growth Factor (bFGF), 20ng/ml Hepatocyte Growth Factor (HGF) and 20ng/ml Bone Morphogenetic Protein 2 (BMP2)). We performed microarray analysis of guided USSC and unmodified USSC to compare the gene expression profile of both cell populations, in order to evaluate whether any specific genes, or gene groups, were involved in mediating this beneficial effect.

ORGANISM(S): Homo sapiens

SUBMITTER: Enda O'Connell

PROVIDER: E-MEXP-3638 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A comparison of the efficacy of transplantation of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction.

Flynn Aidan A Chen Xizhe X O'Connell Enda E O'Brien Timothy T

Stem cell research & therapy 20120913 5

<h4>Introduction</h4>A number of questions remain unanswered in the field of cell therapy for acute myocardial infarction, including what is the optimal cell type, and can therapeutic efficacy be enhanced by conditioning regimens. In this study, we sought to address these questions by directly comparing the effect of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells delivered 24 hours post-myocardial infarction and by determining if the therapeutic efficacy of unrest ...[more]

PMID: 22974654

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Project description:Underdeveloped lungs are the primary cause of death in premature infants, however, little is known about stem and progenitor cell maintenance during human lung development. In this study, we have identified that FGF7, Retinoic Acid and CHIR-99021, a small molecule that inhibits GSK3 to activate Wnt signaling, support in vitro maintenance of primary human fetal lung bud tip progenitor cells in a progenitor state. Furthermore, these factors are sufficient to derive a population of human bud tip-like progenitor cells in 3D organoid structures from human pluripotent stem cells (hPSC). Functional studies showed that hPSC-derived bud tip progenitor organoids do not contain any mesenchymal cell types, maintain multilineage potential in vitro and are able to engraft into the airways of injured mice and respond to systemic factors. We performed RNA-sequencing to assess the degree of similarity in global gene expression profiles between the full human fetal lung (59-127 days gestation), isolated human fetal bud tip progenitors, organoids grown from primary fetal bud tip progenitors, and hPSC-derived bud tip organoids. Results showed that hPSC-derived organoids have molecular profiles similar to organoids generated from primary human fetal lung tissue. Gene expression differences between hPSC-derived bud tip organoids and fetal progenitor organoids may be related to the presence of contaminating mesenchymal cells in primary cultures. hPSC-derived bud tip organoids are generated from a well-defined human cell sources, offering a distinct advantage over rare primary tissue as a means to study human specific lung development, homeostasis and disease.<br>Sample Nomenclature - Description<br> -------------------------------------------------------------------------<br> Peripheral fetal lung the distal/peripheral portion of the fetal lung (i.e., distal 0.5 cm) was excised from the rest of the lung using a scalpel. This includes all components of the lung (e.g., epithelial, mesenchymal, vascular). <br>Isolated fetal bud tip the bud peripheral portion of the fetal lung was excised with a scalpel and subjected to enzymatic digestion and microdissection. The epithelium was dissected and separated from the mesenchyme, but a small amount of associated mesenchyme likely remained. <br>Fetal progenitor organoid 3D organoid structures that arose from culturing isolated fetal epithelial bud tips. <br>Foregut spheroid 3D foregut endoderm structure as described in Dye et al. (2015). Gives rise to patterned lung organoid (PLO) when grown in 3F medium. <br> Patterned lung organoid (PLO) lung organoids that were generated by differentiating hPSCs, as described throughout the manuscript. <br> Bud tip organoid organoids derived from PLOs, enriched for SOX2/SOX9 co-expressing cells, and grown/passaged in 3F medium.

Dataset Information

A Comparison of the Efficacy of Transplantation of Bone Marrow Derived Mesenchymal Stem Cells and Unrestricted Somatic Stem Cells on Outcome After Acute Myocardial Infarction

Publications

A comparison of the efficacy of transplantation of bone marrow-derived mesenchymal stem cells and unrestricted somatic stem cells on outcome after acute myocardial infarction.

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