| First Author | Sun X | Year | 2017 |
| Journal | Redox Biol | Volume | 13 |
| Pages | 196-206 | PubMed ID | 28582728 |
| Mgi Jnum | J:311019 | Mgi Id | MGI:6764910 |
| Doi | 10.1016/j.redox.2017.05.018 | Citation | Sun X, et al. (2017) Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia. Redox Biol 13:196-206 |
| abstractText | The autologous ALDH bright (ALDH(br)) cell therapy for ischemic injury is clinically safe and effective, while the underlying mechanism remains elusive. Here, we demonstrated that the glycolysis dominant metabolism of ALDH(br) cells is permissive to restore blood flow in an ischemic hind limb model compared with bone marrow mononuclear cells (BMNCs). PCR array analysis showed overtly elevated Aldh2 expression of ALDH(br) cells following hypoxic challenge. Notably, ALDH(br) cells therapy induced blood flow recovery in this model was reduced in case of ALDH2 deficiency. Moreover, significantly reduced glycolysis flux and increased reactive oxygen species (ROS) levels were detected in ALDH(br) cell from Aldh2-/- mice. Compromised effect on blood flow recovery was also noticed post transplanting the human ALDH(br) cell from ALDH2 deficient patients (GA or AA genotypes) in this ischemic hindlimb mice model. Taken together, our findings illustrate the indispensable role of ALDH2 in maintaining glycolysis dominant metabolism of ALDH(br) cell and advocate that patient's Aldh2 genotype is a prerequisite for the efficacy of ALDH(br) cell therapy for peripheral ischemia. |
