The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction

Sung Hwan Moon, Sun Woong Kang, Soon Jung Park, Daekyeong Bae, Sungjoon Kim, Hyang Ae Lee, Kyung Soo Kim, Ki Sung Hong, Jong Soo Kim, Jeong Tae Do, Ki Hyun Byun, Hyung Min Chung

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Abstract

Embryonic stem cells (ESCs) have the capacity to undergo directed differentiation into contracting cardiomyocytes. Therefore, functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are potential candidates for cellular cardiomyoplasty to regenerate the myocardium after infarction. However, the directed differentiation of hESCs induces not only contracting cardiomyocytes but also other cell types. Thus, a risk of teratoma formation and oncologic transformation exists following the transplantation of hESC-CMs containing other cell lineages. In addition, the transplantation of hESC-CMs into the infarcted myocardium limits therapeutic efficacy due to low viability and poor engraftment. In this study, we established an efficient preparation method to obtain pure contracting cardiomyocytes from hESCs. We also developed a delivery system to achieve enhanced viability and a functional connection with the host myocardium after transplantation in a myocardial infarction model. A serum-free medium was used to obtain pure contracting cardiomyocytes from other cell lineages after the cardiac differentiation of hESCs. Aggregates of purified hESC-CMs were formed, and then the expression of cardiomyocyte-specific markers and the viability of the aggregated CMs were examined in hypoxic conditions. In addition, we determined whether the viability of the hESC-CMs and their ability to engraft with the host myocardium could be enhanced by transplanting them as aggregates in a myocardial infarction model. The therapeutic efficacy of the cardiomyocytes was examined by immunohistochemical analyses as well as physiological analyses of left-ventricular function. We found that the transplantation of contracting hESC-CM aggregates improved their survival and function in infarcted rat hearts in comparison to the transplantation of dissociated cells. Our method using hESC-CMs can be considered an effective strategy for clinical applications without critical barriers.

Original languageEnglish
Pages (from-to)4013-4026
Number of pages14
JournalBiomaterials
Volume34
Issue number16
DOIs
StatePublished - 1 May 2013

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Stem cells
Cardiac Myocytes
Myocardial Infarction
Serum-Free Culture Media
Myocardium
Rats
Transplantation
Cell Lineage
Human Embryonic Stem Cells
Cardiomyoplasty
Teratoma
Cell Transplantation
Embryonic Stem Cells
Left Ventricular Function
Infarction

Keywords

  • Aggregate
  • Cardiomyocyte
  • Human embryonic stem cell
  • Purification
  • Transplantation

Cite this

Moon, Sung Hwan ; Kang, Sun Woong ; Park, Soon Jung ; Bae, Daekyeong ; Kim, Sungjoon ; Lee, Hyang Ae ; Kim, Kyung Soo ; Hong, Ki Sung ; Kim, Jong Soo ; Do, Jeong Tae ; Byun, Ki Hyun ; Chung, Hyung Min. / The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction. In: Biomaterials. 2013 ; Vol. 34, No. 16. pp. 4013-4026.
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abstract = "Embryonic stem cells (ESCs) have the capacity to undergo directed differentiation into contracting cardiomyocytes. Therefore, functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are potential candidates for cellular cardiomyoplasty to regenerate the myocardium after infarction. However, the directed differentiation of hESCs induces not only contracting cardiomyocytes but also other cell types. Thus, a risk of teratoma formation and oncologic transformation exists following the transplantation of hESC-CMs containing other cell lineages. In addition, the transplantation of hESC-CMs into the infarcted myocardium limits therapeutic efficacy due to low viability and poor engraftment. In this study, we established an efficient preparation method to obtain pure contracting cardiomyocytes from hESCs. We also developed a delivery system to achieve enhanced viability and a functional connection with the host myocardium after transplantation in a myocardial infarction model. A serum-free medium was used to obtain pure contracting cardiomyocytes from other cell lineages after the cardiac differentiation of hESCs. Aggregates of purified hESC-CMs were formed, and then the expression of cardiomyocyte-specific markers and the viability of the aggregated CMs were examined in hypoxic conditions. In addition, we determined whether the viability of the hESC-CMs and their ability to engraft with the host myocardium could be enhanced by transplanting them as aggregates in a myocardial infarction model. The therapeutic efficacy of the cardiomyocytes was examined by immunohistochemical analyses as well as physiological analyses of left-ventricular function. We found that the transplantation of contracting hESC-CM aggregates improved their survival and function in infarcted rat hearts in comparison to the transplantation of dissociated cells. Our method using hESC-CMs can be considered an effective strategy for clinical applications without critical barriers.",
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author = "Moon, {Sung Hwan} and Kang, {Sun Woong} and Park, {Soon Jung} and Daekyeong Bae and Sungjoon Kim and Lee, {Hyang Ae} and Kim, {Kyung Soo} and Hong, {Ki Sung} and Kim, {Jong Soo} and Do, {Jeong Tae} and Byun, {Ki Hyun} and Chung, {Hyung Min}",
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Moon, SH, Kang, SW, Park, SJ, Bae, D, Kim, S, Lee, HA, Kim, KS, Hong, KS, Kim, JS, Do, JT, Byun, KH & Chung, HM 2013, 'The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction', Biomaterials, vol. 34, no. 16, pp. 4013-4026. https://doi.org/10.1016/j.biomaterials.2013.02.022

The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction. / Moon, Sung Hwan; Kang, Sun Woong; Park, Soon Jung; Bae, Daekyeong; Kim, Sungjoon; Lee, Hyang Ae; Kim, Kyung Soo; Hong, Ki Sung; Kim, Jong Soo; Do, Jeong Tae; Byun, Ki Hyun; Chung, Hyung Min.

In: Biomaterials, Vol. 34, No. 16, 01.05.2013, p. 4013-4026.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The use of aggregates of purified cardiomyocytes derived from human ESCs for functional engraftment after myocardial infarction

AU - Moon, Sung Hwan

AU - Kang, Sun Woong

AU - Park, Soon Jung

AU - Bae, Daekyeong

AU - Kim, Sungjoon

AU - Lee, Hyang Ae

AU - Kim, Kyung Soo

AU - Hong, Ki Sung

AU - Kim, Jong Soo

AU - Do, Jeong Tae

AU - Byun, Ki Hyun

AU - Chung, Hyung Min

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Embryonic stem cells (ESCs) have the capacity to undergo directed differentiation into contracting cardiomyocytes. Therefore, functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are potential candidates for cellular cardiomyoplasty to regenerate the myocardium after infarction. However, the directed differentiation of hESCs induces not only contracting cardiomyocytes but also other cell types. Thus, a risk of teratoma formation and oncologic transformation exists following the transplantation of hESC-CMs containing other cell lineages. In addition, the transplantation of hESC-CMs into the infarcted myocardium limits therapeutic efficacy due to low viability and poor engraftment. In this study, we established an efficient preparation method to obtain pure contracting cardiomyocytes from hESCs. We also developed a delivery system to achieve enhanced viability and a functional connection with the host myocardium after transplantation in a myocardial infarction model. A serum-free medium was used to obtain pure contracting cardiomyocytes from other cell lineages after the cardiac differentiation of hESCs. Aggregates of purified hESC-CMs were formed, and then the expression of cardiomyocyte-specific markers and the viability of the aggregated CMs were examined in hypoxic conditions. In addition, we determined whether the viability of the hESC-CMs and their ability to engraft with the host myocardium could be enhanced by transplanting them as aggregates in a myocardial infarction model. The therapeutic efficacy of the cardiomyocytes was examined by immunohistochemical analyses as well as physiological analyses of left-ventricular function. We found that the transplantation of contracting hESC-CM aggregates improved their survival and function in infarcted rat hearts in comparison to the transplantation of dissociated cells. Our method using hESC-CMs can be considered an effective strategy for clinical applications without critical barriers.

AB - Embryonic stem cells (ESCs) have the capacity to undergo directed differentiation into contracting cardiomyocytes. Therefore, functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are potential candidates for cellular cardiomyoplasty to regenerate the myocardium after infarction. However, the directed differentiation of hESCs induces not only contracting cardiomyocytes but also other cell types. Thus, a risk of teratoma formation and oncologic transformation exists following the transplantation of hESC-CMs containing other cell lineages. In addition, the transplantation of hESC-CMs into the infarcted myocardium limits therapeutic efficacy due to low viability and poor engraftment. In this study, we established an efficient preparation method to obtain pure contracting cardiomyocytes from hESCs. We also developed a delivery system to achieve enhanced viability and a functional connection with the host myocardium after transplantation in a myocardial infarction model. A serum-free medium was used to obtain pure contracting cardiomyocytes from other cell lineages after the cardiac differentiation of hESCs. Aggregates of purified hESC-CMs were formed, and then the expression of cardiomyocyte-specific markers and the viability of the aggregated CMs were examined in hypoxic conditions. In addition, we determined whether the viability of the hESC-CMs and their ability to engraft with the host myocardium could be enhanced by transplanting them as aggregates in a myocardial infarction model. The therapeutic efficacy of the cardiomyocytes was examined by immunohistochemical analyses as well as physiological analyses of left-ventricular function. We found that the transplantation of contracting hESC-CM aggregates improved their survival and function in infarcted rat hearts in comparison to the transplantation of dissociated cells. Our method using hESC-CMs can be considered an effective strategy for clinical applications without critical barriers.

KW - Aggregate

KW - Cardiomyocyte

KW - Human embryonic stem cell

KW - Purification

KW - Transplantation

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