Impact of different bone marrow cell preparations on left ventricular remodelling after experimental myocardial
Stefan Frantz1, Duttu Vallabhapurapu, Jochen Tillmanns
1Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius-Maximilians-Universität Würzburg, Germany.
Insights
Unfractionated bone marrow (BM) cells, not specific subsets, partially improved cardiac remodelling after myocardial infarction (MI) in mice. These effects may stem from paracrine signalling, offering insights into BM cell therapy for heart repair.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Bone marrow (BM)-derived hematopoietic stem cells are investigated for myocardial infarction (MI) therapy.
- Inconsistent clinical and experimental data highlight the need to evaluate different BM cell populations.
- Understanding BM cell subset effects is crucial for optimizing cardiac repair strategies.
Purpose of the Study:
- To determine the impact of distinct BM cell populations on left ventricular remodelling post-MI.
- To compare the therapeutic potential of unfractionated BM cells versus specific subsets (Lin+ and Lin-).
- To explore the underlying mechanisms, including paracrine effects, of BM cell therapy.
Main Methods:
- Myocardial infarction induced in female mice via coronary artery ligation.
- Randomized treatment groups: unfractionated BM, Lin+, Lin- cells, or saline.
- Cell engraftment confirmed by Y-chromosome PCR; cardiac function assessed by echocardiography over 6 weeks.
Main Results:
- No significant difference in mortality among treatment groups.
- Left ventricular remodelling was not improved by Lin+ or Lin- cells.
- Unfractionated BM cell injection partially improved cardiac remodelling post-MI.
- Differential regulation of cytokine secretion (e.g., IL-6, GM-CSF) observed in BM cell cultures.
Conclusions:
- Unfractionated BM cells, unlike specific subsets, demonstrated partial efficacy in improving cardiac remodelling after MI.
- Paracrine mechanisms are suggested as a potential mediator of the observed therapeutic effects.
- Findings suggest that the composition of BM cell therapy is critical for cardiac repair outcomes.
Objective:
Bone marrow (BM)-derived haematopoietic stem cells have been proposed as a potential cell source to functionally engraft the myocardium and to improve cardiac function after myocardial infarction (MI). However, experimental and clinical data are inconsistent. Since the specific characteristics of different BM cell subsets could influence their therapeutic potential we determined the effect of different BM cell populations on left ventricular remodelling after MI.
Methods And Results:
MI was induced in female mice by coronary artery ligation. Surviving mice were randomised to receive either: total BM, mature Lin(+) or primitive Lin(-) cells from male mice, or saline, via intracardiac injection. Injected cells were detected in the infarct and border zone by PCR for Y-chromosomal sequences. Serial transthoracic echocardiography was performed 1, 21, and 42 days after MI. Over a period of 6 weeks, mortality was not different between the groups. After MI, animals exhibited left ventricular dilatation, as expected. Left ventricular remodelling was not influenced by Lin(+) or Lin(-) BM cells but was partially improved by unfractionated BM cell injection. Paracrine secretion of cytokines (e.g. IL-6, GM-CSF) was differentially regulated in supernatants of cultured BM cells.
Summary:
Treatment with unfractionated BM cells, but not Lin(+), or Lin(-) cells partially improved cardiac remodelling and function after MI. This may be mediated by paracrine effects.
