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Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential.

Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Sato A, Okada Y, Iida Y, Itoh J, Itoh Y, Kamiguchi H, Kawamoto A, Asahara T - J Am Heart Assoc (2014)

Bottom Line: The resulting cells (QQMNCs) in EPC colony-forming assay generated significantly more definitive EPC colonies than PBMNCs.Using murine ischemic hindlimb models, the efficacy of QQMNC intramuscular transplantation (Tx) was compared to that of PBMNCTx, cultured "early EPC" Tx (eEPCTx), and granulocyte colony-stimulating factor mobilized CD34(+) cell Tx (GmCD34Tx).Laser Doppler imaging revealed the blood perfusion recovery in ischemic hindlimbs after QQMNCTx superior to after PBMNCTx and eEPCTx, but also earlier than after GmCD34Tx.

View Article: PubMed Central - PubMed

Affiliation: Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan (H.M., T.S., A.S., T.A.).

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Blood flow and distribution of limb salvage patterns in ischemic hindlimbs. A and B, Laser Doppler imaging was used to analyze blood flow 21 days after ischemia. Cells were transplanted at 1×104/mouse (5×103 cells/each of ATM and GCM). The top panels show the representative features in each group. ROI for blood flow measurement is shown by a yellow square. The bottom line graph presents percent (%) blood‐flow ratio of ischemic‐to‐contralateral hindlimb during the observation period for 21 days. *P<0.05; **P<0.01 versus IMDM control. #P<0.05 versus PBMNCTx in (A) or eEPCTx in (B). Each line graph represents a mean±SE. N=12 mice/group. C and D, Limb salvage features of QQMNCTx versus PBMNCTx day 21 after ischemia. The top pictures in (C) show the representative features of ischemic leg patterns; the severity of the phenotypes are graded from the left to the right. The column graphs in (C and D) show the respective % distributions of severity for each group. N=19 mice for IMDM control, 21 for PBMNCTx, and 23 for QQMNCTx in (C). N=10 mice per each group in (D). LS, limb salvage; TN, toe necrosis; FN, foot necrosis; AA, autoamputation in (C and D). ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IMDM, Iscove's Modified Dulbecco's Medium; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; ROI, regions of interest.
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fig05: Blood flow and distribution of limb salvage patterns in ischemic hindlimbs. A and B, Laser Doppler imaging was used to analyze blood flow 21 days after ischemia. Cells were transplanted at 1×104/mouse (5×103 cells/each of ATM and GCM). The top panels show the representative features in each group. ROI for blood flow measurement is shown by a yellow square. The bottom line graph presents percent (%) blood‐flow ratio of ischemic‐to‐contralateral hindlimb during the observation period for 21 days. *P<0.05; **P<0.01 versus IMDM control. #P<0.05 versus PBMNCTx in (A) or eEPCTx in (B). Each line graph represents a mean±SE. N=12 mice/group. C and D, Limb salvage features of QQMNCTx versus PBMNCTx day 21 after ischemia. The top pictures in (C) show the representative features of ischemic leg patterns; the severity of the phenotypes are graded from the left to the right. The column graphs in (C and D) show the respective % distributions of severity for each group. N=19 mice for IMDM control, 21 for PBMNCTx, and 23 for QQMNCTx in (C). N=10 mice per each group in (D). LS, limb salvage; TN, toe necrosis; FN, foot necrosis; AA, autoamputation in (C and D). ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IMDM, Iscove's Modified Dulbecco's Medium; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; ROI, regions of interest.

Mentions: We investigated the potential of QQMNCs to treat ischemia, using a mouse ischemic hindlimb model; the effect was evaluated by blood flow measurement for 21 days after ischemic surgery. We compared the effect of QQMNCTx with that of no‐cell Tx (IMDM medium‐injected mice:IMDM control) or PBMNCTx (Figure 5A).


Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential.

Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Sato A, Okada Y, Iida Y, Itoh J, Itoh Y, Kamiguchi H, Kawamoto A, Asahara T - J Am Heart Assoc (2014)

Blood flow and distribution of limb salvage patterns in ischemic hindlimbs. A and B, Laser Doppler imaging was used to analyze blood flow 21 days after ischemia. Cells were transplanted at 1×104/mouse (5×103 cells/each of ATM and GCM). The top panels show the representative features in each group. ROI for blood flow measurement is shown by a yellow square. The bottom line graph presents percent (%) blood‐flow ratio of ischemic‐to‐contralateral hindlimb during the observation period for 21 days. *P<0.05; **P<0.01 versus IMDM control. #P<0.05 versus PBMNCTx in (A) or eEPCTx in (B). Each line graph represents a mean±SE. N=12 mice/group. C and D, Limb salvage features of QQMNCTx versus PBMNCTx day 21 after ischemia. The top pictures in (C) show the representative features of ischemic leg patterns; the severity of the phenotypes are graded from the left to the right. The column graphs in (C and D) show the respective % distributions of severity for each group. N=19 mice for IMDM control, 21 for PBMNCTx, and 23 for QQMNCTx in (C). N=10 mice per each group in (D). LS, limb salvage; TN, toe necrosis; FN, foot necrosis; AA, autoamputation in (C and D). ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IMDM, Iscove's Modified Dulbecco's Medium; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; ROI, regions of interest.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309104&req=5

fig05: Blood flow and distribution of limb salvage patterns in ischemic hindlimbs. A and B, Laser Doppler imaging was used to analyze blood flow 21 days after ischemia. Cells were transplanted at 1×104/mouse (5×103 cells/each of ATM and GCM). The top panels show the representative features in each group. ROI for blood flow measurement is shown by a yellow square. The bottom line graph presents percent (%) blood‐flow ratio of ischemic‐to‐contralateral hindlimb during the observation period for 21 days. *P<0.05; **P<0.01 versus IMDM control. #P<0.05 versus PBMNCTx in (A) or eEPCTx in (B). Each line graph represents a mean±SE. N=12 mice/group. C and D, Limb salvage features of QQMNCTx versus PBMNCTx day 21 after ischemia. The top pictures in (C) show the representative features of ischemic leg patterns; the severity of the phenotypes are graded from the left to the right. The column graphs in (C and D) show the respective % distributions of severity for each group. N=19 mice for IMDM control, 21 for PBMNCTx, and 23 for QQMNCTx in (C). N=10 mice per each group in (D). LS, limb salvage; TN, toe necrosis; FN, foot necrosis; AA, autoamputation in (C and D). ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IMDM, Iscove's Modified Dulbecco's Medium; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; ROI, regions of interest.
Mentions: We investigated the potential of QQMNCs to treat ischemia, using a mouse ischemic hindlimb model; the effect was evaluated by blood flow measurement for 21 days after ischemic surgery. We compared the effect of QQMNCTx with that of no‐cell Tx (IMDM medium‐injected mice:IMDM control) or PBMNCTx (Figure 5A).

Bottom Line: The resulting cells (QQMNCs) in EPC colony-forming assay generated significantly more definitive EPC colonies than PBMNCs.Using murine ischemic hindlimb models, the efficacy of QQMNC intramuscular transplantation (Tx) was compared to that of PBMNCTx, cultured "early EPC" Tx (eEPCTx), and granulocyte colony-stimulating factor mobilized CD34(+) cell Tx (GmCD34Tx).Laser Doppler imaging revealed the blood perfusion recovery in ischemic hindlimbs after QQMNCTx superior to after PBMNCTx and eEPCTx, but also earlier than after GmCD34Tx.

View Article: PubMed Central - PubMed

Affiliation: Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan (H.M., T.S., A.S., T.A.).

Show MeSH
Related in: MedlinePlus