HiPS-Cardiac Trilineage Cell Generation and Transplantation: a Novel Therapy for Myocardial Infarction

Jackson, Ampadu O.; Tang, Huifang; Yin, Kai

doi:10.1007/s12265-019-09891-4

Cited by 7 publications

(3 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro generated cardiomyocytes are an important tool for cardiovascular research, as they can be utilized for disease modelling or for the development of drug screening assays to assess the cardiac toxic risk of established or newly synthesized drugs [37][38][39]. Moreover, promising preclinical data suggests the therapeutic potential of generated cardiomyocytes for the treatment of cardiac diseases to overall improve heart regeneration and function [40,41]. Although several stem cell types are available to produce cardiac cells, the ideal source of stem cells remains elusive as each has its own advantages and drawbacks.…”

Section: Discussionmentioning

confidence: 99%

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

Mueller

Wolfien

Ekat

et al. 2020

Cells

View full text Add to dashboard Cite

Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to embryonic stem cells or induced pluripotent stem cells. Here we used non-integrative methods, including microRNA and mRNA, for cardiac reprogramming of adult MSC derived from bone marrow, dental follicle, and adipose tissue. We found that MSC derived from adipose tissue can partly be reprogrammed into the cardiac lineage by transient overexpression of GATA4, TBX5, MEF2C, and MESP1, while cells isolated from bone marrow, and dental follicle exhibit only weak reprogramming efficiency. qRT-PCR and transcriptomic analysis revealed activation of a cardiac-specific gene program and up-regulation of genes known to promote cardiac development. Although we did not observe the formation of fully mature cardiomyocytes, our data suggests that adult MSC have the capability to acquire a cardiac-like phenotype when treated with mRNA coding for transcription factors that regulate heart development. Yet, further optimization of the reprogramming process is mandatory to increase the reprogramming efficiency.

show abstract

Section: Discussionmentioning

confidence: 99%

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

Mueller

Wolfien

Ekat

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…A variety of stem/progenitor cells are under study that may have the appropriate characteristics to augment or replace cardiac cells lost following infarction. Such potential replacement cells include mesenchymal stem cells (MSCs) [ 7 , 8 , 9 , 10 , 11 , 12 ], c-kit+ cardiac progenitor cells [ 13 , 14 , 15 ], as well as embryonic stem cells (ESCs) [ 16 , 17 , 18 , 19 , 20 ] and induced pluripotent stem cells (iPSCs) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. There are currently more than 583 clinical studies grafting cells into the heart, 129 utilizing MSCs of which 77 are completed, active or recruiting [ 28 , 29 ], and (accessed on 1 December 2021).…”

Section: Introductionmentioning

confidence: 99%

MSC Pretreatment for Improved Transplantation Viability Results in Improved Ventricular Function in Infarcted Hearts

Pittenger

Eghtesad

Sánchez

et al. 2022

IJMS

View full text Add to dashboard Cite

Many clinical studies utilizing MSCs (mesenchymal stem cells, mesenchymal stromal cells, or multipotential stromal cells) are underway in multiple clinical settings; however, the ideal approach to prepare these cells in vitro and to deliver them to injury sites in vivo with maximal effectiveness remains a challenge. Here, pretreating MSCs with agents that block the apoptotic pathways were compared with untreated MSCs. The treatment effects were evaluated in the myocardial infarct setting following direct injection, and physiological parameters were examined at 4 weeks post-infarct in a rat permanent ligation model. The prosurvival treated MSCs were detected in the hearts in greater abundance at 1 week and 4 weeks than the untreated MSCs. The untreated MSCs improved ejection fraction in infarcted hearts from 61% to 77% and the prosurvival treated MSCs further improved ejection fraction to 83% of normal. The untreated MSCs improved fractional shortening in the infarcted heart from 52% to 68%, and the prosurvival treated MSCs further improved fractional shortening to 77% of normal. Further improvements in survival of the MSC dose seems possible. Thus, pretreating MSCs for improved in vivo survival has implications for MSC-based cardiac therapies and in other indications where improved cell survival may improve effectiveness.

show abstract

“…Atherosclerotic plaque rupture with thrombus formation is determined to be the most dominant cause of myocardial infarction, which will result in an acute reduction of blood supply and imbalance in oxygen supply and demand. The prolonged ischemia will cause irreversible myocardial necrosis and heart failure [4][5][6]. To negate the life-threatening condition, rapid diagnoses and the proper therapy to restore the perfusion are urgent to salvage the jeopardized myocardium.…”

Section: Introductionmentioning

confidence: 99%

Integrating Literature-Based Knowledge Database and Expression Data to Explore Molecular Pathways Connecting PPARG and Myocardial Infarction

2020

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor γ (PPARG) might play a protective role in the development of myocardial infarction (MI) with limited mechanisms identified. Genes associated with both PPARG and MI were extracted from Elsevier Pathway Studio to construct the initial network. The gene expression activity within the network was estimated through a mega-analysis with eight independent expression datasets derived from Gene Expression Omnibus (GEO) to build PPARG and MI connecting pathways. After that, gene set enrichment analysis (GSEA) was conducted to explore the functional profile of the genes involved in the PPARG-driven network. PPARG demonstrated a significantly low expression in MI patients (LFC=−0.52; p<1.84e−9). Consequently, PPARG could indicatively be promoting three MI inhibitors (e.g., SOD1, CAV1, and POU5F1) and three MI-downregulated markers (e.g., ALB, ACADM, and ADIPOR2), which were deactivated in MI cases (p<0.05), and inhibit two MI-upregulated markers (RELA and MYD88), which showed increased expression levels in MI cases (p=0.0077 and 0.047, respectively). These eight genes were mainly enriched in nutrient- and cell metabolic-related pathways and functionally linked by GSEA and PPCN. Our results suggest that PPARG could protect the heart against both the development and progress of MI through the regulation of nutrient- and metabolic-related pathways.

show abstract

HiPS-Cardiac Trilineage Cell Generation and Transplantation: a Novel Therapy for Myocardial Infarction

Cited by 7 publications

References 105 publications

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

RNA-Based Strategies for Cardiac Reprogramming of Human Mesenchymal Stromal Cells

MSC Pretreatment for Improved Transplantation Viability Results in Improved Ventricular Function in Infarcted Hearts

Integrating Literature-Based Knowledge Database and Expression Data to Explore Molecular Pathways Connecting PPARG and Myocardial Infarction

Contact Info

Product

Resources

About