Therapeutic angiogenesis by autologous bone-marrow transplantation in a general hospital setting

Taguchi, Akihiko; Ohtani, Masakatsu; Soma, Toshihiro; Watanabe, Masato; Kinosita, N.

doi:10.1053/ejvs.2002.1831

Cited by 34 publications

(20 citation statements)

References 5 publications

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“…We observed that rhIL-11 treatment led to a 20-fold increase in circulating CD34+/VEGFR2+ mononuclear cells and that mobilized CD34+/VEGFR2+ cells home into sites of collateral vessel remodeling resulting in collateral vessel growth and faster recovery of perfusion to ischemic limb in a manner that closely correlated with mobilization of CD34+/VEGFR2+ cells. These observations suggest that rhIL-11-mobilized CD34+/VEGFR2+ mononuclear cells, in part, participate in collateral vessel growth and is consistent with other reports showing a correlation between circulating CD34+ cells and the extent of collateral vessel remodeling during cerebral26 or hindlimb ischemia 27 in human and augmentation of regional blood flow and neovascularization 28 during cerebral or hindlimb ischemia in mice 29, 30.…”

Section: Discussionsupporting

confidence: 91%

Recombinant Human Interleukin-11 Treatment Enhances Collateral Vessel Growth After Femoral Artery Ligation

Aitsebaomo

Srivastava

Zhang

et al. 2011

ATVB

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Objective-To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34 ϩ / vascular endothelial growth factor receptor (VEGFR) 2 ϩ mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia. Methods and Results-We observed that treatment of Sv129 mice with continuous infusion of 200-g/kg rhIL-11 per day led to in vivo mobilization of CD34 ϩ /VEGFR2 ϩ cells that peaked at 72 hours. Sv129 mice pretreated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34 ϩ /VEGFR2 ϩ cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of perivascular CD34 ϩ /VEGFR2 ϩ cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hindlimb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions. Conclusion-These novel findings show that rhIL-11 promotes in vivo mobilization of CD34 ϩ /VEGFR2 ϩ mononuclear cells, enhances collateral vessel growth, and increases recovery of perfusion after femoral artery ligation. Thus, rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease.

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Section: Discussionsupporting

confidence: 91%

Recombinant Human Interleukin-11 Treatment Enhances Collateral Vessel Growth After Femoral Artery Ligation

Aitsebaomo

Srivastava

Zhang

et al. 2011

ATVB

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“…Furthermore, human CD34 + cells were shown to secrete numerous angiogenic factors, including VEGF, HGF, and IGF-1 (4). On the basis of these observations, clinical trials of cell transplantation in hindlimb (5,6) and cardiac ischemia (7) have been initiated with promising results.…”

Section: Introductionmentioning

confidence: 99%

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Taguchi¹,

Soma²,

Tanaka³

et al. 2004

J. Clin. Invest.

334

281

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Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34 + cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34 + cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

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“…The angiogenic effect of these cells appears to be mediated primarily via paracrine cytokine and growth factor signaling, rather than via widespread incorporation of donor progenitor cells into the growing vasculature. The response to intravenous administration of CD34 + cells stimulates both intrinsic angiogenic and neurogenic responses, which appear to be tightly linked (Peterson, 2004;Taguchi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Angiogenic Recruitment of Pericytes from Bone Marrow after Stroke

Kokovay

Cunningham

2006

J Cereb Blood Flow Metab

127

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Bone marrow-derived cells (BMDCs) contribute to revascularization after ischemia. However, the mechanisms by which BMDCs support vessel remodeling after cerebral ischemia are not clear. Using mouse chimeras that express enhanced green fluorescent protein in reconstituted bone marrow, we investigated the role of BMDCs in revascularization and brain repair after middle cerebral artery occlusion of murine brain. After ischemia, two populations of BMDCs were observed, one in the brain parenchyma and another associated with the vasculature. The number of BMDCs that infiltrated the brain parenchyma peaked at 7 days and persisted through 14 days, the last time point observed. The majority of BMDCs were characterized as microglia, based on cell-type-specific marker expression. We observed a robust angiogenic response after cerebral ischemia. Bone marrow-derived cells associated with remodeling blood vessels were negative for endothelial markers, but were surrounded by basal lamina and expressed desmin and vimentin, identifying these cells as pericytes. Quantification of BMDCs that expressed desmin revealed increasing desmin expression with time. Perivascular associated BMDCs that expressed desmin were immunoreactive for the angiogenic factors vascular endothelial growth factor and transforming growth factor-b. These findings suggest that pericytes are recruited from the periphery and are involved in blood vessel stabilization during ischemia-induced angiogenesis.

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Therapeutic angiogenesis by autologous bone-marrow transplantation in a general hospital setting

Cited by 34 publications

References 5 publications

Recombinant Human Interleukin-11 Treatment Enhances Collateral Vessel Growth After Femoral Artery Ligation

Recombinant Human Interleukin-11 Treatment Enhances Collateral Vessel Growth After Femoral Artery Ligation

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Angiogenic Recruitment of Pericytes from Bone Marrow after Stroke

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