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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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Histological evaluation of myogenesis in ischemic hindlimbs. A and C, Representative images of muscle tissues in ATM by H&E staining. (a) Normofused tissue with normal morphology of skeletal muscle fibers with the subsarcolemmal nuclei in contralateral hindlimb of IMDM control, (b) ischemic hindlimbs from IMDM control, (c) PBMNCTx, or (d) QQMNCTx in (A). (a) IMDM control, (b) eEPCTx, (c) QQMNCTx, and (d) GmCD34Tx in (C). Note that the smaller size of the fibers in combination with centrally located nuclei indicated that a muscle fiber had been actively regenerating. B and D, The graphs present the counts of regenerating muscle fibers in each group. **P<0.01; ***P<0.001 versus IMDM control in (B and D). #P<0.05 versus PBMNCTx in (B) or eEPCTx in (D). Each column in the graph represents a mean±SE. ×20 HPF. N=6 mice per group. ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; H&E, hematoxylin and eosin; HPF, high power field; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation.
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fig08: Histological evaluation of myogenesis in ischemic hindlimbs. A and C, Representative images of muscle tissues in ATM by H&E staining. (a) Normofused tissue with normal morphology of skeletal muscle fibers with the subsarcolemmal nuclei in contralateral hindlimb of IMDM control, (b) ischemic hindlimbs from IMDM control, (c) PBMNCTx, or (d) QQMNCTx in (A). (a) IMDM control, (b) eEPCTx, (c) QQMNCTx, and (d) GmCD34Tx in (C). Note that the smaller size of the fibers in combination with centrally located nuclei indicated that a muscle fiber had been actively regenerating. B and D, The graphs present the counts of regenerating muscle fibers in each group. **P<0.01; ***P<0.001 versus IMDM control in (B and D). #P<0.05 versus PBMNCTx in (B) or eEPCTx in (D). Each column in the graph represents a mean±SE. ×20 HPF. N=6 mice per group. ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; H&E, hematoxylin and eosin; HPF, high power field; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation.

Mentions: Muscle fibers with centrally located nuclei indicate myogenesis mediated by fusion of myoblasts in ATM of ischemic hindlimbs; therefore, we determined that the average densities of such regenerating muscle fibers (regenerating muscle fibers/mm2) for the QQMNCTx, PBMNCTx, and control groups were 775.6±113.3, 424.2±47.12, and 398.6±48.42, respectively (Figure 8A and 8B).


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)

Histological evaluation of myogenesis in ischemic hindlimbs. A and C, Representative images of muscle tissues in ATM by H&E staining. (a) Normofused tissue with normal morphology of skeletal muscle fibers with the subsarcolemmal nuclei in contralateral hindlimb of IMDM control, (b) ischemic hindlimbs from IMDM control, (c) PBMNCTx, or (d) QQMNCTx in (A). (a) IMDM control, (b) eEPCTx, (c) QQMNCTx, and (d) GmCD34Tx in (C). Note that the smaller size of the fibers in combination with centrally located nuclei indicated that a muscle fiber had been actively regenerating. B and D, The graphs present the counts of regenerating muscle fibers in each group. **P<0.01; ***P<0.001 versus IMDM control in (B and D). #P<0.05 versus PBMNCTx in (B) or eEPCTx in (D). Each column in the graph represents a mean±SE. ×20 HPF. N=6 mice per group. ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; H&E, hematoxylin and eosin; HPF, high power field; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4309104&req=5

fig08: Histological evaluation of myogenesis in ischemic hindlimbs. A and C, Representative images of muscle tissues in ATM by H&E staining. (a) Normofused tissue with normal morphology of skeletal muscle fibers with the subsarcolemmal nuclei in contralateral hindlimb of IMDM control, (b) ischemic hindlimbs from IMDM control, (c) PBMNCTx, or (d) QQMNCTx in (A). (a) IMDM control, (b) eEPCTx, (c) QQMNCTx, and (d) GmCD34Tx in (C). Note that the smaller size of the fibers in combination with centrally located nuclei indicated that a muscle fiber had been actively regenerating. B and D, The graphs present the counts of regenerating muscle fibers in each group. **P<0.01; ***P<0.001 versus IMDM control in (B and D). #P<0.05 versus PBMNCTx in (B) or eEPCTx in (D). Each column in the graph represents a mean±SE. ×20 HPF. N=6 mice per group. ATM indicates anterior tibial muscle; eEPCTx, early endothelial progenitor cell transplantation; GmCD34, granulocyte colony‐stimulating factor mobilized CD34+ cell; H&E, hematoxylin and eosin; HPF, high power field; PBMNCTx, peripheral blood mononuclear cell transplantation; QQMNCTx, quality and quantity control culture of mononuclear cell transplantation.
Mentions: Muscle fibers with centrally located nuclei indicate myogenesis mediated by fusion of myoblasts in ATM of ischemic hindlimbs; therefore, we determined that the average densities of such regenerating muscle fibers (regenerating muscle fibers/mm2) for the QQMNCTx, PBMNCTx, and control groups were 775.6±113.3, 424.2±47.12, and 398.6±48.42, respectively (Figure 8A and 8B).

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