Mouse bone marrow-derived endothelial progenitor cells do not restore radiation-induced microvascular damage

Area of Science:

• Cardiovascular Research
• Radiation Oncology
• Regenerative Medicine

Background:

• Radiotherapy for breast and thoracic cancers can cause delayed cardiac microvascular damage and increase mortality.
• Restoring microvasculature through endothelial cell proliferation and revascularization is vital for irradiated heart function.
• Bone marrow-derived endothelial progenitor cells (BM-derived EPCs) are investigated for their potential to repair radiation-induced vascular damage.

Purpose of the Study:

• To evaluate the efficacy of BM-derived EPCs in restoring radiation-induced microvascular damage in the heart.
• To assess the impact of endoglin expression on the therapeutic potential of BM-derived EPCs.

Main Methods:

• Adult C57BL/6 mice received cardiac irradiation (16 Gy).
• BM-derived EPCs from Eng(+/+) or Eng(+/-) mice were transplanted 16 and 28 weeks post-irradiation.
• Morphological damage, microvascular density, and fibrosis markers were assessed at 40 weeks.

Main Results:

• Cardiac irradiation reduced microvascular density and increased endothelial damage, indicated by decreased alkaline phosphatase and increased von Willebrand factor.
• BM-derived EPC treatment did not improve microvascular density or reduce endothelial damage.
• However, BM-derived EPCs from both Eng(+/+) and Eng(+/-) mice significantly diminished radiation-induced collagen deposition (fibrosis).

Conclusions:

• BM-derived EPCs do not restore radiation-induced microvascular damage in the heart.
• BM-derived EPCs effectively inhibit radiation-induced cardiac fibrosis.
• Endoglin deficiency in EPCs did not hinder their antifibrotic effect.