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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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Embryonic Stem Cell-Derived Endothelial Cells for Treatment of Hindlimb Ischemia
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Conditioned medium derived from mesenchymal stem cells overexpressing HPV16 E6E7 dramatically improves ischemic limb.

Ming-Chau Chang1, Ching-Hua Tsao2, Wei-Hua Huang3

  • 1Institute of Anatomy, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan; Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan.

Journal of Molecular and Cellular Cardiology
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Summary

Genetically modified mesenchymal stem cells (MSCs) secrete angiogenic factors, including Interleukin-1β and vascular endothelial growth factor A, to improve blood flow and prevent tissue damage in ischemic limbs.

Keywords:
Angiogenic factorsMarrow stromal cellsMultipotent stromal cellsPI3K-AKTParacrine effects

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Area of Science:

  • Stem Cell Biology
  • Angiogenesis Research
  • Molecular Medicine

Background:

  • Mesenchymal stem cells (MSCs) are known to secrete factors that promote angiogenesis.
  • Previous studies showed MSCs expressing HPV16 E6E7 mRNA (E6E7-MSCs) have enhanced longevity and differentiation potential without neoplastic transformation.

Purpose of the Study:

  • To investigate whether E6E7-MSCs secrete molecules that enhance angiogenesis.
  • To determine the specific factors and mechanisms involved in the angiogenic potential of E6E7-MSCs.

Main Methods:

  • Comparison of conditioned medium from E6E7-MSCs (E6E7-CM) and primary MSCs (primary-CM) on endothelial cell function.
  • Analysis of AKT activation and cytokine/growth factor release (IL-1β, VEGFA) from E6E7-MSCs.
  • In vivo assessment of E6E7-CM in a mouse limb ischemia model, including perfusion, histology, and fibrosis evaluation.

Main Results:

  • E6E7-CM significantly enhanced endothelial cell migration and tube formation compared to primary-CM.
  • E6E7-MSCs showed increased AKT activation and release of IL-1β and VEGFA.
  • Neutralization of IL-1β or VEGFA in E6E7-CM abolished its pro-angiogenic effects.
  • E6E7-CM improved blood perfusion, reduced muscle loss and fibrosis, and increased endothelial cell counts in ischemic limbs.

Conclusions:

  • E6E7-MSCs enhance angiogenesis through AKT-mediated secretion of IL-1β and VEGFA.
  • E6E7-CM effectively promotes blood perfusion and tissue preservation in a mouse limb ischemia model.
  • These findings highlight the therapeutic potential of E6E7-MSCs for conditions involving impaired blood supply.