CD117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation

TS Li, K Hamano, M Nishida… - American Journal …, 2003 - journals.physiology.org
TS Li, K Hamano, M Nishida, M Hayashi, H Ito, A Mikamo, M Matsuzaki
American Journal of Physiology-Heart and Circulatory Physiology, 2003journals.physiology.org
Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear
cells. We investigated the roles of mature mononuclear cell and stem cell fractions in bone
marrow in this treatment. Although CD34 is the most popular marker for stem cell selection
for inducing therapeutic angiogenesis, we separated CD117-positive cells (CD117+) from
mature bone marrow mononuclear cells [CD117-negative cells (CD117–)] from mice using
the antibody to the stem cell receptor, because some of the bone marrow stem cells that …
Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells. We investigated the roles of mature mononuclear cell and stem cell fractions in bone marrow in this treatment. Although CD34 is the most popular marker for stem cell selection for inducing therapeutic angiogenesis, we separated CD117-positive cells (CD117+) from mature bone marrow mononuclear cells [CD117-negative cells (CD117)] from mice using the antibody to the stem cell receptor, because some of the bone marrow stem cells that express CD117+ and CD34 might generate angiogenic cytokines and differentiate into endothelial cells. The angiogenic potency of CD117+ and CD117 cells was investigated in vitro and in vivo. Significantly higher levels of VEGF were secreted from the CD117+ cells than from the CD117 cells (P < 0.001). Most of the CD117 cells died, but the CD117+ cells grew well and differentiated into endothelial cells within 14 days of culture. The CD117+ cells survived and were incorporated in microvessels within 14 days of being implanted into the ischemic hindlimbs of mice, but the CD117 cells did not. The microvessel density and blood perfusion of the ischemic hindlimbs were significantly higher in the CD117+ cell-implanted mice than in the CD117 cell-implanted mice (P < 0.01). The microvessel density in ischemic hindlimbs was also significantly higher in the CD117+ cell-implanted mice than in the total bone marrow cell-implanted mice (P < 0.05). Thus CD117+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.
American Physiological Society