Journal Article

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

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

2016

Overview

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 × 10 4 /10 8 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Analysis / Animals / Biomarkers - metabolism / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Bone marrow / CD146 Antigen - genetics / CD146 Antigen - metabolism / Cell Adhesion / Cell Biology / Cells, Cultured / Embryoid Bodies - cytology / Embryoid Bodies - metabolism / Embryoid Bodies - transplantation / Extracellular Matrix - chemistry / Extracellular Matrix - metabolism / Fetal blood / Fetal Blood - cytology / Fetal Blood - metabolism / Gene Expression / Germ Layers - cytology / Germ Layers - growth & development / Germ Layers - metabolism / Hematopoietic stem cells / Humans / Life Sciences / Mesenchymal Stromal Cells - cytology / Mesenchymal Stromal Cells - metabolism / Mice / Mice, Knockout / Muscle, Skeletal - injuries / Octamer Transcription Factor-3 - genetics / Octamer Transcription Factor-3 - metabolism / Regeneration - genetics / Regenerative Medicine/Tissue Engineering / Stem Cells / Stem Cells - cytology / Stem Cells - metabolism