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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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qRT‐PCR assay of murine gene expression in ischemic hindlimbs. The graphs show the relative gene expression levels of promyogenic (MyoD1, myogenin, and IGF‐1), anti‐inflammation (TGF‐β), and proangiogenic (IL‐1β) factors. The comparison of the levels in QQMNCTx to those in IMDM control or PBMNCTx in (A) and in IMDM control, eEPCTx, and GmCD34Tx in (B). H, healthy (contralateral) hindlimb of IMDM control mice. *P<0.05; **P<0.01; ***P<0.001 versus IMDM control. $P<0.0.5; $$P<0.01 versus H. #P<0.05 in (A and B). ##P<0.01; ###P<0.001 versus eEPCTx in (B). Each graph column represents a mean±SE. N=4 to 6 mice per group. eEPCTx indicates early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IGF, insulin‐like growth factor; IL, interleukin; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; qRT‐PCR, quantitative real‐time polymerase chain reaction; TGF, transforming growth factor.
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fig11: qRT‐PCR assay of murine gene expression in ischemic hindlimbs. The graphs show the relative gene expression levels of promyogenic (MyoD1, myogenin, and IGF‐1), anti‐inflammation (TGF‐β), and proangiogenic (IL‐1β) factors. The comparison of the levels in QQMNCTx to those in IMDM control or PBMNCTx in (A) and in IMDM control, eEPCTx, and GmCD34Tx in (B). H, healthy (contralateral) hindlimb of IMDM control mice. *P<0.05; **P<0.01; ***P<0.001 versus IMDM control. $P<0.0.5; $$P<0.01 versus H. #P<0.05 in (A and B). ##P<0.01; ###P<0.001 versus eEPCTx in (B). Each graph column represents a mean±SE. N=4 to 6 mice per group. eEPCTx indicates early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IGF, insulin‐like growth factor; IL, interleukin; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; qRT‐PCR, quantitative real‐time polymerase chain reaction; TGF, transforming growth factor.

Mentions: The relative ratio of each gene expression in PBMNCTx, QQMNCTx, GmCD34Tx, and eEPCTx versus that in IMDM control was as follows: 1.22±0.05, 2.58±0.63, 2.94±0.61, and 1.06±0.08 in MyoD1; 1.90±0.10, 2.94±0.49, 2.69±0.41, and 0.84±0.06 in myogenin; and 1.17±0.11, 2.06±0.40, 2.20±0.56, and 1.00±0.11 in IGF‐1, respectively (Figure 11A and 11B).


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)

qRT‐PCR assay of murine gene expression in ischemic hindlimbs. The graphs show the relative gene expression levels of promyogenic (MyoD1, myogenin, and IGF‐1), anti‐inflammation (TGF‐β), and proangiogenic (IL‐1β) factors. The comparison of the levels in QQMNCTx to those in IMDM control or PBMNCTx in (A) and in IMDM control, eEPCTx, and GmCD34Tx in (B). H, healthy (contralateral) hindlimb of IMDM control mice. *P<0.05; **P<0.01; ***P<0.001 versus IMDM control. $P<0.0.5; $$P<0.01 versus H. #P<0.05 in (A and B). ##P<0.01; ###P<0.001 versus eEPCTx in (B). Each graph column represents a mean±SE. N=4 to 6 mice per group. eEPCTx indicates early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IGF, insulin‐like growth factor; IL, interleukin; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; qRT‐PCR, quantitative real‐time polymerase chain reaction; TGF, transforming growth factor.
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fig11: qRT‐PCR assay of murine gene expression in ischemic hindlimbs. The graphs show the relative gene expression levels of promyogenic (MyoD1, myogenin, and IGF‐1), anti‐inflammation (TGF‐β), and proangiogenic (IL‐1β) factors. The comparison of the levels in QQMNCTx to those in IMDM control or PBMNCTx in (A) and in IMDM control, eEPCTx, and GmCD34Tx in (B). H, healthy (contralateral) hindlimb of IMDM control mice. *P<0.05; **P<0.01; ***P<0.001 versus IMDM control. $P<0.0.5; $$P<0.01 versus H. #P<0.05 in (A and B). ##P<0.01; ###P<0.001 versus eEPCTx in (B). Each graph column represents a mean±SE. N=4 to 6 mice per group. eEPCTx indicates early endothelial progenitor cell transplantation; GCM, gastrocunemius muscle; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; IGF, insulin‐like growth factor; IL, interleukin; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation; qRT‐PCR, quantitative real‐time polymerase chain reaction; TGF, transforming growth factor.
Mentions: The relative ratio of each gene expression in PBMNCTx, QQMNCTx, GmCD34Tx, and eEPCTx versus that in IMDM control was as follows: 1.22±0.05, 2.58±0.63, 2.94±0.61, and 1.06±0.08 in MyoD1; 1.90±0.10, 2.94±0.49, 2.69±0.41, and 0.84±0.06 in myogenin; and 1.17±0.11, 2.06±0.40, 2.20±0.56, and 1.00±0.11 in IGF‐1, respectively (Figure 11A and 11B).

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