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

Abstract

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.

Regeneration of Infarcted Myocardium by Intramyocardial Implantation of Ex Vivo Transforming Growth Factor-β–Preprogrammed Bone Marrow Stem Cells

“…Although the intramyocardial implantation of CD117 ϩ /Lin Ϫ bone marrow stem cells can regenerate infarcted myocardium effectively, 7 we separated the total CD117 ϩ bone marrow stem cells, because more than 80% of the separated CD117 ϩ cells are lineage-negative, and the remaining CD117 ϩ /Lin ϩ cells are considered a valuable subpopulation for inducing angiogenesis to improve regional perfusion in the infarcted myocardium. 14 In fact, the significant increase in microvessel density in our preprogrammed and untreated groups clearly demonstrated that the implantation of CD117 ϩ stem cells into the infarcted myocardium has the potential to induce therapeutic angiogenesis. This significant increase in microvessel density in both the preprogrammed and untreated groups contributed, at least in part, to ).…”

“…14 Briefly, bone marrow mononuclear cells collected from the femur and tibia of mice were incubated with PE-conjugated anti-mouse CD117 (c-kit) antibody (Bioscience) for 30 minutes on ice. After washing with PBS, cells were incubated with anti-PE microbeads (Miltenyi Biotec) for 20 minutes.…”

“…To detect the myogenic and osteoblast differentiation of CD117 ϩ cells induced by TGF-␤ 1 , immunostaining was performed with mouse anti-myosin, ventricular heavy chain ␣/␤ monoclonal antibody (Chemicon Inc) and goat anti-mouse osteocalcin (Chemicon Inc), followed by incubation with FITC or R-PE-conjugated secondary antibodies, after 3 and 7 days of cultivation. 14 …”

Seeding density is a crucial determinant for the in vivo vascularisation capacity of adipose tissue-derived microvascular fragments

“…In addition, the isolated ad-MVF had a comparable average length and cellular composition. Of interest, the ad-MVF did not only contain CD31 + endothelial cells and α-SMA + perivascular cells, but also cells expressing the stem cell surface markers CD90 and CD117, which have been reported to exhibit a high regenerative and angiogenic potential (Li et al, 2003;Li et al, 2005;Oishi and Ito-Dufros, 2006).…”

Histological changes after implantation of autologous bone marrow mononuclear cells for chronic critical limb ischemia

“…It is noteworthy that endothelial cells express c-kit whose importance in angiogenesis has been outlined. 2,3 Tateishi et al 1 have previously shown CD31 þ endothelial cells expressing Ki-67 in muscle samples of a CLI patient who died 3.2 months after implantation of BM-MNC, suggesting the presence of proliferating endothelial cells in newly formed vessels. The origin of these cells remains to be determined: did they belong to implanted cells?…”