Parthenogenetic stem cells for tissue-engineered heart repair

Michael Didié, Peter Christalla, Michael Rubart, Vijayakumar Muppala, Stephan Döker, Bernhard Unsöld, Ali El-Armouche, Thomas Rau, Thomas Eschenhagen, Alexander P. Schwoerer, Heimo Ehmke, Udo Schumacher, Sigrid Fuchs, Claudia Lange, Alexander Becker, Wen Tao, John A. Scherschel, Mark H. Soonpaa, Tao Yang, Qiong LinMartin Zenke, Dong Wook Han, Hans R. Schöler, Cornelia Rudolph, Doris Steinemann, Brigitte Schlegelberger, Steve Kattman, Alec Witty, Gordon Keller, Loren J. Field, Wolfram Hubertus Zimmermann

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.

Original languageEnglish (US)
Pages (from-to)1285-1298
Number of pages14
JournalJournal of Clinical Investigation
Volume123
Issue number3
DOIs
StatePublished - Mar 1 2013

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Stem Cells
Cardiac Myocytes
Embryonic Stem Cells
Major Histocompatibility Complex
Myocardium
Pluripotent Stem Cells
Organogenesis
Blastocyst
Fertilization in Vitro
Cell- and Tissue-Based Therapy
Epigenomics
Documentation
Myocardial Infarction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Didié, M., Christalla, P., Rubart, M., Muppala, V., Döker, S., Unsöld, B., ... Zimmermann, W. H. (2013). Parthenogenetic stem cells for tissue-engineered heart repair. Journal of Clinical Investigation, 123(3), 1285-1298. https://doi.org/10.1172/JCI66854

Parthenogenetic stem cells for tissue-engineered heart repair. / Didié, Michael; Christalla, Peter; Rubart, Michael; Muppala, Vijayakumar; Döker, Stephan; Unsöld, Bernhard; El-Armouche, Ali; Rau, Thomas; Eschenhagen, Thomas; Schwoerer, Alexander P.; Ehmke, Heimo; Schumacher, Udo; Fuchs, Sigrid; Lange, Claudia; Becker, Alexander; Tao, Wen; Scherschel, John A.; Soonpaa, Mark H.; Yang, Tao; Lin, Qiong; Zenke, Martin; Han, Dong Wook; Schöler, Hans R.; Rudolph, Cornelia; Steinemann, Doris; Schlegelberger, Brigitte; Kattman, Steve; Witty, Alec; Keller, Gordon; Field, Loren J.; Zimmermann, Wolfram Hubertus.

In: Journal of Clinical Investigation, Vol. 123, No. 3, 01.03.2013, p. 1285-1298.

Research output: Contribution to journalArticle

Didié, M, Christalla, P, Rubart, M, Muppala, V, Döker, S, Unsöld, B, El-Armouche, A, Rau, T, Eschenhagen, T, Schwoerer, AP, Ehmke, H, Schumacher, U, Fuchs, S, Lange, C, Becker, A, Tao, W, Scherschel, JA, Soonpaa, MH, Yang, T, Lin, Q, Zenke, M, Han, DW, Schöler, HR, Rudolph, C, Steinemann, D, Schlegelberger, B, Kattman, S, Witty, A, Keller, G, Field, LJ & Zimmermann, WH 2013, 'Parthenogenetic stem cells for tissue-engineered heart repair', Journal of Clinical Investigation, vol. 123, no. 3, pp. 1285-1298. https://doi.org/10.1172/JCI66854
Didié M, Christalla P, Rubart M, Muppala V, Döker S, Unsöld B et al. Parthenogenetic stem cells for tissue-engineered heart repair. Journal of Clinical Investigation. 2013 Mar 1;123(3):1285-1298. https://doi.org/10.1172/JCI66854
Didié, Michael ; Christalla, Peter ; Rubart, Michael ; Muppala, Vijayakumar ; Döker, Stephan ; Unsöld, Bernhard ; El-Armouche, Ali ; Rau, Thomas ; Eschenhagen, Thomas ; Schwoerer, Alexander P. ; Ehmke, Heimo ; Schumacher, Udo ; Fuchs, Sigrid ; Lange, Claudia ; Becker, Alexander ; Tao, Wen ; Scherschel, John A. ; Soonpaa, Mark H. ; Yang, Tao ; Lin, Qiong ; Zenke, Martin ; Han, Dong Wook ; Schöler, Hans R. ; Rudolph, Cornelia ; Steinemann, Doris ; Schlegelberger, Brigitte ; Kattman, Steve ; Witty, Alec ; Keller, Gordon ; Field, Loren J. ; Zimmermann, Wolfram Hubertus. / Parthenogenetic stem cells for tissue-engineered heart repair. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 3. pp. 1285-1298.
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AU - Lange, Claudia

AU - Becker, Alexander

AU - Tao, Wen

AU - Scherschel, John A.

AU - Soonpaa, Mark H.

AU - Yang, Tao

AU - Lin, Qiong

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AU - Han, Dong Wook

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AU - Rudolph, Cornelia

AU - Steinemann, Doris

AU - Schlegelberger, Brigitte

AU - Kattman, Steve

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