P4027Safety and high-grade myocardial uptake of Whartons Jelly Plurioptent Stem Cells transcoronary transfer in acute myocardial infarction in man

Musiałek, Piotr; Mazurek, Adam; Kwiecien, E; Drabik, Leszek; Tekieli, Łukasz; Szot, Wojciech; Kostkiewicz, Magdalena; Jarocha, Danuta; Banyś, Robert; Urbanczyk, M; Płazak, Wojciech; Olszowska, Maria; Żmudka, Krzysztof; Podolec, Piotr; Majka, Marcin; Circulate,

doi:10.1093/eurheartj/ehx504.p4027

Cited by 6 publications

(6 citation statements)

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“…Despite these obstacles, the level of LVEF improvement seen with cell-based therapies is comparable to that seen with other pharmacological treatments [159]. Cellular therapies can promote cardiac repair and regenerate lost myocardial precursor cells, but they do not appear to improve myocardial contractility, according to one specific criticism.…”

Section: )mentioning

confidence: 97%

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

et al. 2022

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Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.

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Section: )mentioning

confidence: 97%

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

et al. 2022

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“…The results of numerous important studies in humans confirm observations from animal model concerning cell retention and distribution. Table III provides the most relevant data from studies in humans in which SPECT was used [29,34,[62][63][64][65][66][67][68][69][70][71].…”

Section: Human Studiesmentioning

confidence: 99%

“…It was also found that retention of progenitor cells occurs preferentially in the (viable) peri-infarct zone, suggesting that the infarct zone is largely inaccessible to transcoronary-administered cells [29]. Moreover, the coronary-non-occlusive method delivery of Wharton's jelly mesenchymal stem cells (WJMSCs -combining high angiogenic and cardiogenic potential with low immunogenicity) showed a high and reproducible retention rate (30%) of 99 Tc-labeled WJMSCs in the peri-infarct zone in humans after recent myocardial infarction [62].…”

Section: Mtc -Technetium 99m Hmpao -Hexamethylpropyleneamine Oxime Ch...mentioning

confidence: 99%

“…Moreover, the coronary-non-occlusive method delivery of Wharton’s jelly mesenchymal stem cells (WJMSCs – combining high angiogenic and cardiogenic potential with low immunogenicity) showed a high and reproducible retention rate (30%) of 99 Tc-labeled WJMSCs in the peri-infarct zone in humans after recent myocardial infarction [ 62 ].…”

Section: Human Studiesmentioning

confidence: 99%

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Single-photon emission computed tomography as a fundamental tool in evaluation of myocardial reparation and regeneration therapies

Tekieli¹,

Szot²,

Kwiecień³

et al. 2022

pwki

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Despite unquestionable progress in interventional and pharmacologic therapies of ischemic heart disease, the number of patients with chronic ischemic heart failure is increasing and the prognosis remains poor. Repair/restoration of functional myocardium through progenitor cell-mediated (PCs) healing and renovation of injured myocardium is one of the pivotal directions in biomedical research. PCs release numerous pro-angiogenic and anti-apoptotic factors. Moreover, they have self-renewal capability and may differentiate into specialized cells that include endothelial cells and cardiomyocytes. Uptake and homing of PCs in the zone(s) of ischaemic injury (i.e., their effective transplantation to the target zone) is an essential pre-requisite for any potential therapeutic effect; thus effective cell tracking is fundamental in pre-clinical and early clinical studies. Another crucial requirement in rigorous research is quantification of the infarct zone, including the amount of non-perfused and hypo-perfused myocardium. Quantitative and reproducible evaluation of global and regional myocardial contractility and left ventricular remodeling is particularly relevant in clinical studies. Using SPECT, our earlier work has addressed several critical questions in cardiac regenerative medicine including optimizing transcoronary cell delivery, determination of the zone(s) of myocardial cell uptake, and late functional improvement in relation to the magnitude of cell uptake. Here, we review the role of single-photon emission computed tomography (SPECT), a technique that offers high-sensitivity, quantitative cell tracking on top of its ability to evaluate myocardial perfusion and function on both cross-sectional and longitudinal bases. SPECT, with its direct relevance to routine clinical practice, is a fundamental tool in evaluation of myocardial reparation and regeneration therapies.

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“…Although the functional benefits that have been attained clinically are modest and inconsistent (2), mesenchymal stem cells (MSCs) have gained more and more attention in clinical trials targeting a range of diseases, including heart-related diseases (3)(4)(5). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have emerged as ideal cells for the treatment of MI (3,6).…”

Section: Introductionmentioning

confidence: 99%

A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction

Wang,

Yang,

et al. 2024

Front. Immunol.

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BackgroundTreatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs.Materials and methodshUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server.Result3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs.ConclusionClinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as “division of labor” mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).

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P4027Safety and high-grade myocardial uptake of Whartons Jelly Plurioptent Stem Cells transcoronary transfer in acute myocardial infarction in man

Cited by 6 publications

References 0 publications

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Single-photon emission computed tomography as a fundamental tool in evaluation of myocardial reparation and regeneration therapies

A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction

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