Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts

Eliana Cecilia Martinez Valencia, Duc Thang Vu, Jing Wang, Shera Lilyanna, Lieng H. Ling, Shu U. Gan, Ai Li Tan, Thang T. Phan, Chuen N. Lee, Theo Kofidis

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A crucial question in post-ischemic cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5×104 human CL-MSC coated with 2×103 human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n=8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly.

Original languageEnglish (US)
Pages (from-to)3087-3099
Number of pages13
JournalStem Cells and Development
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

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Video-Assisted Thoracic Surgery
Myocardial Revascularization
Mesenchymal Stromal Cells
Transplants
Fibrin
Cell Survival
Human Umbilical Vein Endothelial Cells
Thoracotomy
Cell- and Tissue-Based Therapy
Cardiac Output
Cicatrix
Blood Vessels
Fibrosis
Heart Failure
Myocardial Infarction
Blood Pressure
Wounds and Injuries

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts. / Martinez Valencia, Eliana Cecilia; Vu, Duc Thang; Wang, Jing; Lilyanna, Shera; Ling, Lieng H.; Gan, Shu U.; Tan, Ai Li; Phan, Thang T.; Lee, Chuen N.; Kofidis, Theo.

In: Stem Cells and Development, Vol. 22, No. 23, 01.12.2013, p. 3087-3099.

Research output: Contribution to journalArticle

Martinez Valencia, Eliana Cecilia ; Vu, Duc Thang ; Wang, Jing ; Lilyanna, Shera ; Ling, Lieng H. ; Gan, Shu U. ; Tan, Ai Li ; Phan, Thang T. ; Lee, Chuen N. ; Kofidis, Theo. / Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts. In: Stem Cells and Development. 2013 ; Vol. 22, No. 23. pp. 3087-3099.
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abstract = "A crucial question in post-ischemic cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5×104 human CL-MSC coated with 2×103 human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n=8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1{\%} and 6.2{\%} enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly.",
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AU - Lilyanna, Shera

AU - Ling, Lieng H.

AU - Gan, Shu U.

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AU - Kofidis, Theo

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