Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction.

Tan SH, Loo SJ, Gao Y, Tao ZH, Su LP, Wang CX, Zhang SL, Mu YH, Cui YH, Abdurrachim D, Wang WH, Lalic J and 6 more

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Lim KC, Bu J, Tan RS, Lee TH, Zhang J, Ye L

Theranostics26 Jun 2021Cited by 47 (Europe PMC)

PMID34335970PMCIDPMC8315077DOI10.7150/thno.56757PepBankPUB-34335970

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Summary

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts. However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown. Here, we determined whether thymosin β4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI). Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro. After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs. Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI. Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation. In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size. hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs. Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.

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

Results from this study13

4 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Efficacy outcome
In cultured hiPSC-CMs, 600 ng/mL of Tb4 protected the cells from hypoxic damage.
In plain wordsIn cells, Tb4 protected stem-cell heart cells from damage caused by low oxygen.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseProtection of hiPSC-CMs from hypoxic damage
Study
humann: not reported in source
hiPSC-CMs under hypoxia
Outcome group
Cell viability and death · Cardiovascular
Studied dose
600 ng/mLAs given in this study (human).
Source sentences
Summary
In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage
Show in the study text Report a problemFND-3433597009
02LabIn vitro (cells)Mechanism
In cultured hiPSC-CMs, 600 ng/mL of Tb4 upregulated AKT activity and BcL-XL.
In plain wordsIn cells, Tb4 raised AKT activity and BcL-XL in stem-cell heart cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseAKT activity and BcL-XL
Study
humann: not reported in source
hiPSC-CMs under hypoxia
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
600 ng/mLAs given in this study (human).
Source sentences
Summary
In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation.
Show in the study text Report a problemFND-3433597010
03LabIn vitro (cells)Efficacy outcome
In cultured cells, 600 ng/mL of Tb4 promoted hiPSC-CM proliferation.
In plain wordsIn cells, Tb4 increased the growth of stem-cell heart cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasehiPSC-CM proliferation
Study
humann: not reported in source
hiPSC-CMs
Outcome group
Cell viability and death · Cardiovascular
Studied dose
600 ng/mLAs given in this study (human).
Source sentences
Summary
In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation.
Show in the study text Report a problemFND-3433597011
04LabIn vitro (cells)Efficacy outcome
In cultured cells, 600 ng/mL of Tb4 promoted hiPSC-EC proliferation.
In plain wordsIn cells, Tb4 increased the growth of stem-cell blood vessel lining cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasehiPSC-EC proliferation
Study
humann: not reported in source
hiPSC-ECs
Outcome group
Cell viability and death · Cardiovascular
Studied dose
600 ng/mLAs given in this study (human).
Source sentences
Summary
In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation.
Show in the study text Report a problemFND-3433597012

Studies that did not test the peptide alone9

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).

05AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, with stem-cell heart cells, improved how well the cells took hold versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasehiPSC-CM engraftment
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597001
06AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 induced vasculogenesis compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, given with stem-cell heart cells, increased new blood vessel formation versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseVasculogenesis
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Angiogenesis · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597002
07AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 induced proliferation of cardiomyocytes compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, given with stem-cell heart cells, increased heart muscle cell growth versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCardiomyocyte proliferation
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597003
08AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 induced proliferation of endothelial cells compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, given with stem-cell heart cells, increased blood vessel lining cell growth versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseEndothelial cell proliferation
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Angiogenesis · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597004
09AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 improved left ventricular systolic function compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, given with stem-cell heart cells, improved the heart's pumping function versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseLeft ventricular systolic function
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597005
10AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In infarcted pigs, co-treatment with Tb4 reduced infarct size compared with hiPSC-CM transplantation alone.
In plain wordsIn pigs after a heart attack, gelatin beads that release Tβ4, with stem-cell heart cells, reduced the damaged area versus cells alone.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseInfarct size
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Comparator
hiPSC-CM transplantation alone
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size.
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597006
11AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Safety outcome
In immunosuppressed infarcted pigs, hiPSC-CM implantation did not increase the incidence of ventricular arrhythmia.
In plain wordsIn pigs with a heart attack, implanting stem-cell heart cells did not increase dangerous heart rhythm problems.
Peptide
Thymosin beta-4 (human)
Outcome
No significant changeVentricular arrhythmia incidence after hiPSC-CM implantation
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Outcome group
Adverse events · Cardiovascular
Source sentences
Summary
hiPSC-CM implantation did not increase incidence of ventricular arrhythmia
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597007
12AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Safety outcome
In immunosuppressed infarcted pigs, hiPSC-CM implantation did not induce tumorigenesis.
In plain wordsIn pigs with a heart attack, implanting stem-cell heart cells did not cause tumors.
Peptide
Thymosin beta-4 (human)
Outcome
No significant changeTumorigenesis after hiPSC-CM implantation
Study
pign: not reported in source
Porcine model of acute myocardial infarction
Outcome group
Adverse events · Cardiovascular
Source sentences
Summary
hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs.
1 context sentence(design, population, supporting numbers)
Summary · context
After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 10⁸ hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs.
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-3433597008
13LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cell-free)Pharmacokinetics
In vitro, gelatin microspheres extended the duration of Tb4 delivery for up to two weeks.
In plain wordsIn lab tests, gelatin microspheres kept releasing Tb4 for up to two weeks.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableDuration of Tb4 delivery from gelatin microspheres
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro.
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-3433597013

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

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