Vasoprotective effects of human CD34+ cells: towards clinical applications.
BACKGROUND
The development of cell-based therapeutics for humans requires preclinical testing in animal models. The use of autologous animal products fails to address the efficacy of similar products derived from humans. We used a novel immunodeficient rat carotid injury model in order to determine whether human cells could improve vascular remodelling following acute injury.


METHODS
Human CD34+ cells were separated from peripheral buffy coats using automatic magnetic cell separation. Carotid arterial injury was performed in male Sprague-Dawley nude rats using a 2F Fogarty balloon catheter. Freshly harvested CD34+ cells or saline alone was administered locally for 20 minutes by endoluminal instillation. Structural and functional analysis of the arteries was performed 28 days later.


RESULTS
Morphometric analysis demonstrated that human CD34+ cell delivery was associated with a significant reduction in intimal formation 4 weeks following balloon injury as compared with saline (I/M ratio 0.79 +/- 0.18, and 1.71 +/- 0.18 for CD34, and saline-treated vessels, respectively P < 0.05). Vasoreactivity studies showed that maximal relaxation of vessel rings from human CD34+ treated animals was significantly enhanced compared with saline-treated counterparts (74.1 +/- 10.2, and 36.8 +/- 12.1% relaxation for CD34+ cells and saline, respectively, P < 0.05)


CONCLUSIONS
Delivery of human CD34+ cells limits neointima formation and improves arterial reactivity after vascular injury. These studies advance the concept of cell delivery to effect vascular remodeling toward a potential human cellular product.
Kiernan
Thomas J
TJ
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. kiernan.thomas@mayo.edu
Boilson
Barry A
BA
Witt
Tyra A
TA
Dietz
Allan B
AB
Lerman
Amir
A
Simari
Robert D
RD
D000818:Animals; D018952:Antigens, CD34 / Q000008:administration & dosage* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000628:therapy*; D002404:Catheterization / Q000009:adverse effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000254:growth & development; D006801:Humans; D018189:Immunomagnetic Separation; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology*; D008297:Male; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology; D014664:Vasodilation / Q000502:physiology
D018952:Antigens, CD34; D015415:Biomarkers