Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells

Mitsutoshi Yamada, Bjarki Johannesson, Ido Sagi, Lisa Cole Burnett, Daniel H. Kort, Robert W. Prosser, Daniel Paull, Michael W. Nestor, Matthew Freeby, Ellen Greenberg, Robin S. Goland, Rudolph L. Leibel, Susan L. Solomon, Nissim Benvenisty, Mark V. Sauer, Dieter Egli

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

Original languageEnglish
Pages (from-to)533-536
Number of pages4
JournalNature
Volume510
Issue number7506
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Diploidy
Oocytes
Embryonic Stem Cells
Sendai virus
Blastocyst
Calcium
Cell Line
Induced Pluripotent Stem Cells
Histone Deacetylase Inhibitors
Cell Fusion
Metaphase
Cell- and Tissue-Based Therapy
Cell Nucleus
Gonadotropins
Type 1 Diabetes Mellitus
Transcription Factors
Phosphotransferases
Stem Cells
Cell Culture Techniques

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Yamada, M., Johannesson, B., Sagi, I., Burnett, L. C., Kort, D. H., Prosser, R. W., ... Egli, D. (2014). Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. Nature, 510(7506), 533-536. https://doi.org/10.1038/nature13287

Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. / Yamada, Mitsutoshi; Johannesson, Bjarki; Sagi, Ido; Burnett, Lisa Cole; Kort, Daniel H.; Prosser, Robert W.; Paull, Daniel; Nestor, Michael W.; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S.; Leibel, Rudolph L.; Solomon, Susan L.; Benvenisty, Nissim; Sauer, Mark V.; Egli, Dieter.

In: Nature, Vol. 510, No. 7506, 2014, p. 533-536.

Research output: Contribution to journalArticle

Yamada, M, Johannesson, B, Sagi, I, Burnett, LC, Kort, DH, Prosser, RW, Paull, D, Nestor, MW, Freeby, M, Greenberg, E, Goland, RS, Leibel, RL, Solomon, SL, Benvenisty, N, Sauer, MV & Egli, D 2014, 'Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells', Nature, vol. 510, no. 7506, pp. 533-536. https://doi.org/10.1038/nature13287
Yamada, Mitsutoshi ; Johannesson, Bjarki ; Sagi, Ido ; Burnett, Lisa Cole ; Kort, Daniel H. ; Prosser, Robert W. ; Paull, Daniel ; Nestor, Michael W. ; Freeby, Matthew ; Greenberg, Ellen ; Goland, Robin S. ; Leibel, Rudolph L. ; Solomon, Susan L. ; Benvenisty, Nissim ; Sauer, Mark V. ; Egli, Dieter. / Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. In: Nature. 2014 ; Vol. 510, No. 7506. pp. 533-536.
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