Abstract

Recent evidence suggests that mononuclear cells (MNCs) derived from bone marrow and cord blood can differentiate into mesenchymal stem cells (MSCs) or outgrowth endothelial cells (OECs). However, controversy exists as to whether MNCs have the pluripotent capacity to differentiate into MSCs or OECs or are a mixture of cell lineage-determined progenitors of MSCs or OECs. Here, using CD133+/C-kit+/Lin− mononuclear cells (CKL− cells) isolated from human umbilical cord blood using magnetic cell sorting, we characterized the potency of MNC differentiation. We first found that CKL− cells cultured with conditioned medium of OECs or MSCs differentiated into OECs or MSCs and this differentiation was also induced by cell-to-cell contact. When we cultured single CKL− cells on OEC- or MSC-conditioned medium, the cells differentiated morphologically and genetically into OEC- or MSC-like cells, respectively. Moreover, we confirmed that OECs or MSCs differentiated from CKL− cells had the ability to form capillary-like structures in Matrigel and differentiate into osteoblasts, chondrocytes, and adipocytes. Finally, using microarray analysis, we identified specific factors of OECs or MSCs that could potentially be involved in the differentiation fate of CKL− cells. Together, these results suggest that cord blood-derived CKL− cells possess at least bipotential differentiation capacity toward MSCs or OECs.

Highlights

  • Stem cells are a current focus of scientific research due to their plasticity and extensive self-renewal capacity and ability to differentiate into one or more committed descendants, including fully functional mature cells [1]

  • As we found that CKL− mononuclear cells (MNCs) differentiation depended on environmental factors such as the presence of specific cell types or conditioned medium, we hypothesized that soluble factor genes highly expressed in mesenchymal stem cells (MSCs) or outgrowth endothelial cells (OECs) could determine CKL− cell differentiation fate

  • Based on gene expression profiling, we found that MSCs showed high gene expression of WNT5A, CXCL5, vascular endothelial growth factor (VEGF), CCL20, angiopoietin 1 (ANGPT1), growth differentiation factor 5 (GDF5), and WNT5B, whereas OECs showed high gene expression of Jagged 1 (JAG1), JAG2, placental growth factor (PGF), endothelial cell-specific molecule 1 (ESM1), MDK, inhibin beta A (INHBA), growth differentiation factor-3 (GDF3), pre-B-cell colony-enhancing factor 1 (PBEF1), endothelin 1 (EDN1), interleukin 32 (IL32), heparin-binding EGF-like growth factor (HBEGF), CXCL1, CCL2, CCL14, CCL15, bone morphogenetic protein 2 (BMP2), BMP4, and BMP6

Read more

Summary

Introduction

Stem cells are a current focus of scientific research due to their plasticity and extensive self-renewal capacity and ability to differentiate into one or more committed descendants, including fully functional mature cells [1]. Stem cells can differentiate into many cell types, such as cardiomyocytes, vascular cells, neurons, and hepatocytes, both in vitro and in vivo For this reason, regenerative medicine has become a potential therapy for degenerative diseases such as myocardial infarction, vascular diseases, motor neuron diseases, neurodegenerative diseases, and liver disease [2,3,4,5,6,7]. Regenerative medicine has become a potential therapy for degenerative diseases such as myocardial infarction, vascular diseases, motor neuron diseases, neurodegenerative diseases, and liver disease [2,3,4,5,6,7] Classified according to their origin, stem cells may be embryonic stem cells, tissue-specific stem cells, mesenchymal stem cells (MSCs), or induced pluripotent stem cells. MSCs are capable of differentiating into cells of different connective tissue lineages, such as bone, Stem Cells International cartilage, and adipose tissue [10], the mechanisms underlying the differentiation of stem cells derived from human cord blood into MSCs or OECs are not fully understood

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call