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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.

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Characterization of human CD34+ cells. A. Scatter analysis reveals a low side scatter and low to intermediate forward scatter population in keeping with small round cells, as shown in (B) photomicrograph (200×). C. FACS analysis of isolated cells. CD34+ cells express CD45dim and CD133 but not VEGFR2.
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Figure 1: Characterization of human CD34+ cells. A. Scatter analysis reveals a low side scatter and low to intermediate forward scatter population in keeping with small round cells, as shown in (B) photomicrograph (200×). C. FACS analysis of isolated cells. CD34+ cells express CD45dim and CD133 but not VEGFR2.

Mentions: Human CD34+ cells (1 to 3 × 106 CD34+ cells) were obtained from normal human donors using two sequential positive magnetic automated cell separations (MACS) immediately upon receipt of blood sample. Freshly isolated CD34+ cells from blood (purity 87 ± 13%) uniformly expressed CD45dim while 61 ± 9% of cells expressed CD133 and less than 1% of CD34+ cells were positive for VEGFR2 (Figure 1).


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)

Characterization of human CD34+ cells. A. Scatter analysis reveals a low side scatter and low to intermediate forward scatter population in keeping with small round cells, as shown in (B) photomicrograph (200×). C. FACS analysis of isolated cells. CD34+ cells express CD45dim and CD133 but not VEGFR2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Characterization of human CD34+ cells. A. Scatter analysis reveals a low side scatter and low to intermediate forward scatter population in keeping with small round cells, as shown in (B) photomicrograph (200×). C. FACS analysis of isolated cells. CD34+ cells express CD45dim and CD133 but not VEGFR2.
Mentions: Human CD34+ cells (1 to 3 × 106 CD34+ cells) were obtained from normal human donors using two sequential positive magnetic automated cell separations (MACS) immediately upon receipt of blood sample. Freshly isolated CD34+ cells from blood (purity 87 ± 13%) uniformly expressed CD45dim while 61 ± 9% of cells expressed CD133 and less than 1% of CD34+ cells were positive for VEGFR2 (Figure 1).

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