Int J Oral Biol.  2011 Sep;36(3):117-122.

Blood Vessel Regeneration using Human Umbilical Cord-derived Endothelial Progenitor Cells in Cyclophosphamide-treated Immune-deficient Mice

Affiliations
  • 1Lab of Dental Regenerative Biotechnology Major, School of Dentistry, Seoul National University, Korea. jcho@snu.ac.kr
  • 2Dental Research Institute, Seoul National University, Korea.
  • 3Graduate School of Immunology, College of Medicine, Seoul National University, Korea.
  • 4Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Korea.

Abstract

Endothelial cells are a vital constituent of most mammalian organs and are required to maintain the integrity of these tissues. These cells also play a major role in angiogenesis, inflammatory reactions, and in the regulation of thrombosis. Angiogenesis facilitates pulp formation and produces the vessels which are essential for the maintenance of tooth homeostasis. These vessels can also be used in bone and tissue regeneration, and in surgical procedures to place implants or to remove cancerous tissue. Furthermore, endothelial cell regeneration is the most critical component of the tooth generation process. The aim of the present study was to stimulate endothelial regeneration at a site of acute cyclophosphamide (CP)-induced endothelial injury by treatment with human umbilical cord-derived endothelial/mesenchymal stem cells (hEPCs). We randomly assigned 16 to 20-week-old female NOD/SCID mice into three separate groups, a hEPC (1 x 10(5) cells) transplanted, 300mg/kg CP treated and saline (control) group. The mice were sacrificed on days 5 and 10 and blood was collected via the abdominal aorta for analysis. The alanine transaminase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (s-ALP), and albumin (ALB) levels were then evaluated. Tissue sections from the livers and kidneys were stained with hematoxylin and eosin (HE) for microscopic analysis and were subjected to immunohistochemistry to evaluate any changes in the endothelial layer. CP treatment caused a weight reduction after one day. The kidney/body weight ratio increased in the hEPC treated animals compared with the CP only group at 10 days. Moreover, hEPC treatment resulted in reduced s-ALP, AST, ALT levels compared with the CP only group at 10 days. The CP only animals further showed endothelial injuries at five days which were recovered by hEPC treatment at 10 days. The number of CD31-positive cells was increased by hEPC treatment at both 5 and 10 days. In conclusion, the CP-induced disruption of endothelial cells is recovered by hEPC treatment, indicating that hEPC transplantation has potential benefits in the treatment of endothelial damage.

Keyword

human umbilical cord derived endothelial progenitor cell; cyclophosphamide; stem cell transplantation; endothelial injury; regeneration

MeSH Terms

Alanine Transaminase
Alkaline Phosphatase
Animals
Aorta, Abdominal
Aspartate Aminotransferases
Blood Vessels
Cyclophosphamide
Endothelial Cells
Eosine Yellowish-(YS)
Female
Glycosaminoglycans
Hematoxylin
Homeostasis
Humans
Hypogonadism
Immunohistochemistry
Kidney
Liver
Mice
Mitochondrial Diseases
Ophthalmoplegia
Regeneration
Stem Cell Transplantation
Stem Cells
Thrombosis
Tooth
Transplants
Weight Loss
Alanine Transaminase
Alkaline Phosphatase
Aspartate Aminotransferases
Cyclophosphamide
Eosine Yellowish-(YS)
Glycosaminoglycans
Hematoxylin
Hypogonadism
Mitochondrial Diseases
Ophthalmoplegia
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