Living myocardial slices as a model for testing cardiac pro-reparative gene therapies.

Caliandro R, Husetić A, Ligtermoet ML, Boender AR, Zentilin L, Boink GJJ, Giacca M, Gladka MM

Molecular therapy : the journal of the American Society of Gene Therapy25 Mar 2025Cited by 6 (Europe PMC)

PMID40143546PMCIDPMC12266023DOI10.1016/j.ymthe.2025.03.033PepBankPUB-40143546

Summary

Available models currently adopted for preclinical studies in the cardiovascular field either fail to recapitulate human cardiac physiology or are extremely expensive and time-consuming. Translational research would greatly benefit from the development of novel models that reflect the native mature phenotype of the human heart while being cost and time effective. Living myocardial slices (LMSs) have emerged as a novel, powerful ex vivo tool for translational research. Although the number of studies adopting LMSs is rapidly increasing, this model remains largely under-characterized. In this study, we make use of LMSs and compare them to a murine model to deliver the cardioprotective factor zinc finger E box-binding homeobox 2 (ZEB2), a transcription factor known to exert cardioprotective effects after ischemic injury and promote the secretion of pro-angiogenetic factors thymosin beta-4 (TMSB4) and prothymosin alpha (PTMA). Our data show that viral-mediated delivery of these factors induced similar cardiomyocyte gene expression changes in LMS and mouse models. We also show that the delivery of these pro-angiogenic factors enhances an angiogenic response in both models, indicating that LMSs are a suitable alternative to mice for studying the effects of gene transfer in various cardiac cell types.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

01AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In mice, viral delivery of ZEB2, TMSB4 and PTMA enhanced an angiogenic response.
In plain wordsIn mice, delivery of a mix of pro-angiogenic factors that included thymosin beta‑4 enhanced blood vessel growth signals.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseAngiogenic response in mice
Study
mousen: not reported in source
Outcome group
Angiogenesis · Cardiovascular
Source sentences
Summary
We also show that the delivery of these pro-angiogenic factors enhances an angiogenic response in both models, indicating that LMSs are a suitable alternative to mice for studying the effects of gene transfer in various cardiac cell types.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4014354602
02LabNot a test of Thymosin beta-4 (human) aloneEx vivo tissueMechanism
In living myocardial slices, viral delivery of ZEB2, TMSB4 and PTMA enhanced an angiogenic response.
In plain wordsIn heart tissue slices, delivery of a mix of pro-angiogenic factors that included thymosin beta‑4 enhanced blood vessel growth signals.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseAngiogenic response in living myocardial slices
Study
n: not reported in source
Outcome group
Angiogenesis · Cardiovascular
Source sentences
Summary
We also show that the delivery of these pro-angiogenic factors enhances an angiogenic response in both models, indicating that LMSs are a suitable alternative to mice for studying the effects of gene transfer in various cardiac cell types.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4014354601
03LabNot a test of Thymosin beta-4 (human) aloneEx vivo tissueMechanism
Viral delivery of the factors induced similar cardiomyocyte gene expression changes in living myocardial slices and in mouse models.
In plain wordsA mix of factors that included thymosin beta‑4 changed gene activity in heart cells in a similar way in tissue slices and in mice.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableCardiomyocyte gene expression changes
Study
n: not reported in source
Comparator
Mouse model
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
Our data show that viral-mediated delivery of these factors induced similar cardiomyocyte gene expression changes in LMS and mouse models.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-4014354603

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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