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Establishment of Human cell Type-Specific iPS cells with Enhanced Chondrogenic Potential

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Abstract

The propensity of induced pluripotent stem (iPS) cells to differentiate into specific lineages may be influenced by a number of factors, including the selection of the somatic cell type used for reprogramming. Herein we report the generation of new iPS cells, which we derived from human articular chondrocytes and from cord blood mononucleocytes via lentiviral-mediated delivery of Oct4, Klf4, Sox2, and cMyc. Molecular, cytochemical, and cytogenic analyses confirmed the acquisition of hallmark features of pluripotency, as well as the retention of normal karyotypes following reprogramming of both the human articular chondrocytes (AC) and the cord blood (CB) cells. In vitro and in vivo functional analyses formally established the pluripotent differentiation capacity of all cell lines. Chondrogenic differentiation assays comparing iPS cells derived from AC, CB, and a well established dermal fibroblast cell line (HDFa-Yk26) identified enhanced proteoglycan-rich matrix formation and cartilage-associated gene expression from AC-derived iPS cells. These findings suggest that the tissue of origin may impact the fate potential of iPS cells for differentiating into specialized cell types, such as chondrocytes. Thus, we generated new cellular tools for the identification of inherent features driving high chondrogenic potential of reprogrammed cells.

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Abbreviations

AC:

articular chondrocytes

ALP:

alkaline phosphatase

BMP-2:

bone morphogenetic protein-2

CB:

cord blood

DMEM:

Dulbecco’s modified Eagle’s medium

EB:

embryoid bodies

ESC:

embryonic stem cell

iPS cells:

induced pluripotent stem cells

MEFs:

mouse embryonic fibroblasts

SF:

skin fibroblasts

SR:

serum replacement

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Acknowledgments

This work was funded by the State of Connecticut Stem Cell Seed Grants (#10SCA36 and #13-SCA-UCHC-11 to RMG) and the State of Connecticut Established Investigator Grant (#11SCB08 to HD). The authors are grateful for the stem cell services and technical support provided by Leann Crandall, Tiwanna Johnson and Jung Park from the University of Connecticut Stem Cell Core and Chromosome Facility We also acknowledge Dr. Judy Brown and Dr. Rachel O’Neil from the University of Connecticut Induced Pluripotent Stem Cell Core and Chromosome Facility for their expertise with chromosome analyses. The authors have no conflict of interest to declare.

Conflicts of Interest

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT, 06030, USA

    Rosa M. Guzzo, Vanessa Scanlon, Archana Sanjay & Hicham Drissi

  2. Department of Genetics and Developmental Biology, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT, 06030, USA

    Ren-He Xu & Hicham Drissi

  3. Stem Cell Institute, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT, 06030, USA

    Rosa M. Guzzo, Ren-He Xu & Hicham Drissi

  4. Faculty of Health Sciences, University of Macau, Av. Padre Tomas Pereira, Taipa, Macau, China

    Ren-He Xu

Authors
  1. Rosa M. Guzzo
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  2. Vanessa Scanlon
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  3. Archana Sanjay
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  4. Ren-He Xu
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  5. Hicham Drissi
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Corresponding author

Correspondence to Rosa M. Guzzo.

Additional information

This study was funded by the State of Connecticut Stem Cell Program/Department of Public Health. Contract grant numbers: #10SCA36 and #13-SCA-UCHC-11 (to RMG), #11SCB08 (to HD)

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Guzzo, R.M., Scanlon, V., Sanjay, A. et al. Establishment of Human cell Type-Specific iPS cells with Enhanced Chondrogenic Potential. Stem Cell Rev and Rep 10, 820–829 (2014). https://doi.org/10.1007/s12015-014-9538-8

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