Abstract
Transplantation of peripheral blood mononuclear cells (PBMNCs) is a promising therapeutic approach for the treatment of hindlimb ischemia. However, insufficient angiogenesis in ischemic hindlimb after cell transplantation reduces the importance and practicality of this approach. Previously, we demonstrated using mouse models that hypoxic preconditioning augmented the cellular functions of rodent PBMNCs, such as increased cell adhesion capacity and accelerated neovascularization in ischemic hindlimb. To test the clinical application of this therapeutic strategy in this study, we investigated whether the protocol of hypoxic preconditioning, which was established in a condition of 2% O2 for 24 h, can be made available for human PBMNCs (hPBMNCs). In addition, we grafted preconditioned hPBMNCs in a hindlimb ischemia mouse model. Hypoxic preconditioning enhanced cell adhesion capacity and oxidative stress resistance in hPBMNCs. We also observed an up-regulation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in hPBMNCs by hypoxic preconditioning. Furthermore, preconditioned hPBMNCs significantly recovered limb blood flow in ischemic mice after transplantation. These results indicate that our established preconditioning protocol is available for hPBMNCs to effectively reinforce multiple cellular functions. Taken together with our series of study, we believe that this simple but powerful therapeutic strategy will be helpful in curing patients with severe hindlimb ischemia.
| Original language | English |
|---|---|
| Pages (from-to) | 570-579 |
| Number of pages | 10 |
| Journal | American Journal of Translational Research |
| Volume | 6 |
| Issue number | 5 |
| Publication status | Published - 2014 |
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Keywords
- Cell-Based therapy
- Hindlimb ischemia
- Human peripheral blood mononuclear cells
- Hypoxic preconditioning
- Therapeutic angiogenesis
ASJC Scopus subject areas
- Medicine(all)
- Cancer Research
- Clinical Biochemistry
- Molecular Medicine
Cite this
Hypoxically preconditioned human peripheral blood mononuclear cells improve blood flow in hindlimb ischemia xenograft model. / Kudo, Tomoaki; Kubo, Masayuki; Katsura, Shunsaku; Nishimoto, Arata; Ueno, Koji; Samura, Makoto; Fujii, Yasuhiko; Hosoyama, Tohru; Hamano, Kimikazu.
In: American Journal of Translational Research, Vol. 6, No. 5, 2014, p. 570-579.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypoxically preconditioned human peripheral blood mononuclear cells improve blood flow in hindlimb ischemia xenograft model
AU - Kudo, Tomoaki
AU - Kubo, Masayuki
AU - Katsura, Shunsaku
AU - Nishimoto, Arata
AU - Ueno, Koji
AU - Samura, Makoto
AU - Fujii, Yasuhiko
AU - Hosoyama, Tohru
AU - Hamano, Kimikazu
PY - 2014
Y1 - 2014
N2 - Transplantation of peripheral blood mononuclear cells (PBMNCs) is a promising therapeutic approach for the treatment of hindlimb ischemia. However, insufficient angiogenesis in ischemic hindlimb after cell transplantation reduces the importance and practicality of this approach. Previously, we demonstrated using mouse models that hypoxic preconditioning augmented the cellular functions of rodent PBMNCs, such as increased cell adhesion capacity and accelerated neovascularization in ischemic hindlimb. To test the clinical application of this therapeutic strategy in this study, we investigated whether the protocol of hypoxic preconditioning, which was established in a condition of 2% O2 for 24 h, can be made available for human PBMNCs (hPBMNCs). In addition, we grafted preconditioned hPBMNCs in a hindlimb ischemia mouse model. Hypoxic preconditioning enhanced cell adhesion capacity and oxidative stress resistance in hPBMNCs. We also observed an up-regulation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in hPBMNCs by hypoxic preconditioning. Furthermore, preconditioned hPBMNCs significantly recovered limb blood flow in ischemic mice after transplantation. These results indicate that our established preconditioning protocol is available for hPBMNCs to effectively reinforce multiple cellular functions. Taken together with our series of study, we believe that this simple but powerful therapeutic strategy will be helpful in curing patients with severe hindlimb ischemia.
AB - Transplantation of peripheral blood mononuclear cells (PBMNCs) is a promising therapeutic approach for the treatment of hindlimb ischemia. However, insufficient angiogenesis in ischemic hindlimb after cell transplantation reduces the importance and practicality of this approach. Previously, we demonstrated using mouse models that hypoxic preconditioning augmented the cellular functions of rodent PBMNCs, such as increased cell adhesion capacity and accelerated neovascularization in ischemic hindlimb. To test the clinical application of this therapeutic strategy in this study, we investigated whether the protocol of hypoxic preconditioning, which was established in a condition of 2% O2 for 24 h, can be made available for human PBMNCs (hPBMNCs). In addition, we grafted preconditioned hPBMNCs in a hindlimb ischemia mouse model. Hypoxic preconditioning enhanced cell adhesion capacity and oxidative stress resistance in hPBMNCs. We also observed an up-regulation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in hPBMNCs by hypoxic preconditioning. Furthermore, preconditioned hPBMNCs significantly recovered limb blood flow in ischemic mice after transplantation. These results indicate that our established preconditioning protocol is available for hPBMNCs to effectively reinforce multiple cellular functions. Taken together with our series of study, we believe that this simple but powerful therapeutic strategy will be helpful in curing patients with severe hindlimb ischemia.
KW - Cell-Based therapy
KW - Hindlimb ischemia
KW - Human peripheral blood mononuclear cells
KW - Hypoxic preconditioning
KW - Therapeutic angiogenesis
UR - http://www.scopus.com/inward/record.url?scp=84908066867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908066867&partnerID=8YFLogxK
M3 - Article
VL - 6
SP - 570
EP - 579
JO - American Journal of Translational Research
JF - American Journal of Translational Research
SN - 1943-8141
IS - 5
ER -