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Related Concept Videos

Mesenchymal Stem Cells01:19

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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
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Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells.

Yomna Soliman1,2, Gülin Baran1, Nur Mustafaoğlu1,3

  • 1Molecular Biology, Genetics, and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, İstanbul, Turkiye.

Turkish Journal of Biology = Turk Biyoloji Dergisi
|March 13, 2026
PubMed
Summary

Mesenchymal stem cells (MSCs) were directly differentiated into brain-like endothelial cells (BLECs) using a novel protocol. This streamlined method bypasses mesodermal induction, creating a valuable in vitro blood-brain barrier (BBB) model.

Keywords:
Brain microvascular endothelial cells (BMECs)cobalt chloride (CoCl2)mesenchymal stem cells (MSCs)retinoic acid (RA)sodium sulfite (Na2SO3)

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Area of Science:

  • Stem cell biology
  • Neuroscience
  • Endothelial cell biology

Background:

  • Brain microvascular endothelial cells (BMECs) form the blood-brain barrier (BBB), crucial for CNS homeostasis.
  • Mesenchymal stem cells (MSCs), of mesodermal origin, are a potential source for BMEC differentiation.
  • Current human induced pluripotent stem cell (hiPSC) to BMEC protocols require two steps: mesodermal and endothelial induction.

Purpose of the Study:

  • To develop a streamlined protocol for differentiating MSCs directly into brain-like endothelial cells (BLECs).
  • To circumvent the conventional mesodermal induction step for BMEC differentiation.
  • To establish a robust in vitro BBB model using MSC-derived BLECs.

Main Methods:

  • MSC differentiation induced by hypoxia, retinoic acid (RA), cobalt chloride (CoCl2), and sodium sulfite (Na2SO3).
  • Optimization of differentiation media (IMDM, EGM-2, Endopan) and supplements (B27, FBS).
  • Assessment of MSC viability (MTT assay) and BLEC functionality (tube formation assay).

Main Results:

  • Immunocytochemistry confirmed expression of BMEC markers (ZO-1, CD31, occludin) in differentiated cells.
  • The resulting cells exhibited phenotypic and functional characteristics of brain microvascular endothelium.
  • The protocol successfully generated BLECs from MSCs without a mesodermal induction step.

Conclusions:

  • A novel, streamlined MSC-based protocol efficiently differentiates cells into BLECs.
  • This method bypasses the need for mesodermal induction, simplifying BMEC generation.
  • The resulting in vitro BBB model is physiologically relevant for neurological disease research and drug screening.