Umbilical cord blood-derived non-hematopoietic stem cells retrieved and expanded on bone marrow-derived extracellular matrix display pluripotent characteristics

Junjie Wu, Yun Sun, Travis J. Block, Milos Marinkovic, Zhi Liang Zhang, Richard Chen, Yixia Yin, Juquan Song, David D. Dean, Zhongding Lu, Xiao Dong Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces. Methods and results: In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic. Using a native extracellular matrix (ECM), produced by bone marrow (BM) stromal cells, the majority of the UCB-NHSCs attached within 4 h. The colony-forming unit fibroblast frequency of these cells was 1.5 × 104/108 mononuclear cells, which is at least 4000-fold greater than previously reported for UCB-NHSCs. The phenotype of these cells was fibroblast-like and different from those obtained by plastic adhesion; they formed embryonic body-like clusters that were OCT4-positive and expressed other human embryonic stem cell-related markers. Importantly, when implanted subcutaneously for 8 weeks into immunocompromised mice, these ECM-adherent and expanded NHSCs generated three germ layer-derived human tissues including muscle, fat, blood vessel, bone, gland, and nerve. Moreover, injection of these cells into muscle damaged by cryoinjury significantly accelerated muscle regeneration. Conclusions: These results indicate that UCB may be a virtually unlimited source of NHSCs when combined with isolation and expansion on ECM. NHSCs may be a practical alternative to embryonic stem cells for a number of therapeutic applications.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalStem Cell Research and Therapy
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Fingerprint

Stem cells
Fetal Blood
Extracellular Matrix
Bone
Blood
Stem Cells
Bone Marrow
Plastics
Muscle
Fibroblasts
Cell Count
Tissue Adhesions
Adhesion
Germ Layers
Muscles
Cell Separation
Embryonic Stem Cells
Hematopoietic Stem Cells
Tissue culture
Mesenchymal Stromal Cells

Keywords

  • CD146-positive cells
  • Extracellular matrix
  • Extracellular matrix-adherent cells
  • Plastic non-adherent cells
  • Pluripotent stem cells
  • Three germ layer tissue formation in vivo
  • Umbilical cord blood

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Cite this

Umbilical cord blood-derived non-hematopoietic stem cells retrieved and expanded on bone marrow-derived extracellular matrix display pluripotent characteristics. / Wu, Junjie; Sun, Yun; Block, Travis J.; Marinkovic, Milos; Zhang, Zhi Liang; Chen, Richard; Yin, Yixia; Song, Juquan; Dean, David D.; Lu, Zhongding; Chen, Xiao Dong.

In: Stem Cell Research and Therapy, Vol. 7, No. 1, 01.12.2016, p. 1-14.

Research output: Contribution to journalArticle

Wu, Junjie ; Sun, Yun ; Block, Travis J. ; Marinkovic, Milos ; Zhang, Zhi Liang ; Chen, Richard ; Yin, Yixia ; Song, Juquan ; Dean, David D. ; Lu, Zhongding ; Chen, Xiao Dong. / Umbilical cord blood-derived non-hematopoietic stem cells retrieved and expanded on bone marrow-derived extracellular matrix display pluripotent characteristics. In: Stem Cell Research and Therapy. 2016 ; Vol. 7, No. 1. pp. 1-14.
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abstract = "Background: Umbilical cord blood (UCB) not only contains hematopoietic stem cells (HSCs), but also non-hematopoietic stem cells (NHSCs) that are able to differentiate into a number of distinct cell types. Based on studies published to date, the frequency of NHSCs in UCB is believed to be very low. However, the isolation of these cells is primarily based on their adhesion to tissue culture plastic surfaces. Methods and results: In the current study, we demonstrate that this approach overlooks some of the extremely immature NHSCs because they lack the ability to adhere to plastic. Using a native extracellular matrix (ECM), produced by bone marrow (BM) stromal cells, the majority of the UCB-NHSCs attached within 4 h. The colony-forming unit fibroblast frequency of these cells was 1.5 × 104/108 mononuclear cells, which is at least 4000-fold greater than previously reported for UCB-NHSCs. The phenotype of these cells was fibroblast-like and different from those obtained by plastic adhesion; they formed embryonic body-like clusters that were OCT4-positive and expressed other human embryonic stem cell-related markers. Importantly, when implanted subcutaneously for 8 weeks into immunocompromised mice, these ECM-adherent and expanded NHSCs generated three germ layer-derived human tissues including muscle, fat, blood vessel, bone, gland, and nerve. Moreover, injection of these cells into muscle damaged by cryoinjury significantly accelerated muscle regeneration. Conclusions: These results indicate that UCB may be a virtually unlimited source of NHSCs when combined with isolation and expansion on ECM. NHSCs may be a practical alternative to embryonic stem cells for a number of therapeutic applications.",
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AU - Zhang, Zhi Liang

AU - Chen, Richard

AU - Yin, Yixia

AU - Song, Juquan

AU - Dean, David D.

AU - Lu, Zhongding

AU - Chen, Xiao Dong

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