Limits...
Vasoprotective effects of human CD34+ cells: towards clinical applications.

Kiernan TJ, Boilson BA, Witt TA, Dietz AB, Lerman A, Simari RD - J Transl Med (2009)

Bottom Line: 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) 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. kiernan.thomas@mayo.edu

ABSTRACT

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)

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Cell delivery improves vasoreactivity. Human CD34+ cell delivery improves endothelium-dependent vasoreactivity after arterial injury. Carotid rings from CD34+ cell treated rats (open squares) show markedly enhanced vasoreactivity to acetylcholine 4 weeks after injury compared to saline controls (diamonds)(P < 0.05 for CD34+ cells vs. saline). However, uninjured left carotid arteries retained the largest relaxation responses (P < 0.05, vs. CD34+ treated rings). Values are means ± SE. n = 8/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2724497&req=5

Figure 3: Cell delivery improves vasoreactivity. Human CD34+ cell delivery improves endothelium-dependent vasoreactivity after arterial injury. Carotid rings from CD34+ cell treated rats (open squares) show markedly enhanced vasoreactivity to acetylcholine 4 weeks after injury compared to saline controls (diamonds)(P < 0.05 for CD34+ cells vs. saline). However, uninjured left carotid arteries retained the largest relaxation responses (P < 0.05, vs. CD34+ treated rings). Values are means ± SE. n = 8/group.

Mentions: Four weeks after balloon injury and local delivery of CD34+ cells or saline, animals were euthanized and carotids immediately immersed in cold Krebs solution. Following pre-contraction with phenylephrine in an organ chamber, relaxation in response to incremental doses of acetylcholine was assessed (Figure 3). 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 for CD34+ cells vs. saline). The concentration (-Log M) of acetylcholine required to achieve 25% of maximal relaxation (EC25) was 7.19 ± 0.04 in CD34 treated animals compared with 5.38 ± 0.06 in saline treated animals (p < 0.005). Although the data clearly demonstrates that CD34+ cell delivery enhanced endothelium dependent vasorelaxation, responses did not achieve those of uninjured vessels which retained the largest responses to acetylcholine (p < 0.05 for maximal relaxation and EC50 compared with CD34 treatment).


Vasoprotective effects of human CD34+ cells: towards clinical applications.

Kiernan TJ, Boilson BA, Witt TA, Dietz AB, Lerman A, Simari RD - J Transl Med (2009)

Cell delivery improves vasoreactivity. Human CD34+ cell delivery improves endothelium-dependent vasoreactivity after arterial injury. Carotid rings from CD34+ cell treated rats (open squares) show markedly enhanced vasoreactivity to acetylcholine 4 weeks after injury compared to saline controls (diamonds)(P < 0.05 for CD34+ cells vs. saline). However, uninjured left carotid arteries retained the largest relaxation responses (P < 0.05, vs. CD34+ treated rings). Values are means ± SE. n = 8/group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724497&req=5

Figure 3: Cell delivery improves vasoreactivity. Human CD34+ cell delivery improves endothelium-dependent vasoreactivity after arterial injury. Carotid rings from CD34+ cell treated rats (open squares) show markedly enhanced vasoreactivity to acetylcholine 4 weeks after injury compared to saline controls (diamonds)(P < 0.05 for CD34+ cells vs. saline). However, uninjured left carotid arteries retained the largest relaxation responses (P < 0.05, vs. CD34+ treated rings). Values are means ± SE. n = 8/group.
Mentions: Four weeks after balloon injury and local delivery of CD34+ cells or saline, animals were euthanized and carotids immediately immersed in cold Krebs solution. Following pre-contraction with phenylephrine in an organ chamber, relaxation in response to incremental doses of acetylcholine was assessed (Figure 3). 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 for CD34+ cells vs. saline). The concentration (-Log M) of acetylcholine required to achieve 25% of maximal relaxation (EC25) was 7.19 ± 0.04 in CD34 treated animals compared with 5.38 ± 0.06 in saline treated animals (p < 0.005). Although the data clearly demonstrates that CD34+ cell delivery enhanced endothelium dependent vasorelaxation, responses did not achieve those of uninjured vessels which retained the largest responses to acetylcholine (p < 0.05 for maximal relaxation and EC50 compared with CD34 treatment).

Bottom Line: 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) 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. kiernan.thomas@mayo.edu

ABSTRACT

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)

Conclusion: 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.

Show MeSH
Related in: MedlinePlus