Augmentation of Postnatal Neovascularization With Autologous Bone Marrow Transplantation

Shintani, Satoshi; Murohara, Toyoaki; Ikeda, Hisao; Ueno, Takayoshi; Sasaki, Ken-ichiro; Duan, Jun‐Li; Imaizumi, Tsutomu

doi:10.1161/01.cir.103.6.897

Cited by 431 publications

(322 citation statements)

References 41 publications

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“…We and other investigators recently reported that transplantation of culture-expanded human EPCs augmented ischemia-induced angiogenesis in vivo (Kalka et al, 2000;Murohara et al, 2000). Similarly, direct implantation of autologous BM-MNCs containing EPCs has been shown to augment angiogenesis in ischemic tissues (Shintani et al, 2001b, Tateishi-Yuyama et al, 2002. Thus, cell transplantation appears to be an effective means for therapeutic neovascularization.…”

Section: Discussionmentioning

confidence: 78%

Hypoxic Preconditioning Augments Efficacy of Human Endothelial Progenitor Cells for Therapeutic Neovascularization

Akita

Murohara

Ikeda

et al. 2003

Laboratory Investigation

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SUMMARY:A subset of human peripheral blood mononuclear cells (PB-MNCs) differentiate into endothelial progenitor cells (EPCs) that participate in postnatal neovascularization. Although tissue ischemia can mobilize EPCs from bone marrow, the effects of hypoxia on differentiation and angiogenic function of EPCs are little known. We examined whether hypoxic conditioning would modulate differentiation and function of human PB-MNC-derived EPCs. A subset of PB-MNCs gave rise to EPC-like attaching (AT) cells under either normoxic or hypoxic conditions. However, hypoxia much enhanced the differentiation of AT cells from PB-MNCs compared with normoxia. AT cells released vascular endothelial growth factor (VEGF) protein and expressed CD31 and kinase insert domain receptor/VEGFR-2, endothelial lineage markers, on their surface, which were also enhanced by hypoxia. Both a neutralizing anti-VEGF mAb and a KDR-specific receptor tyrosine kinase inhibitor, SU1498, suppressed PB-MNC differentiation into EPC-like AT cells in a dose-dependent manner. Migration of AT cells in response to VEGF as examined by a modified Boyden chamber apparatus was also enhanced by hypoxia. Finally, in vivo neovascularization efficacy was significantly enhanced by in vitro hypoxic conditioning of AT cells when cells were transplanted into the ischemic hindlimb of immunodeficient nude rats. In conclusion, hypoxia directly stimulated differentiation of EPC-like AT cells from human PB-MNC culture. Moreover, hypoxic preconditioning of AT cells before in vivo transplantation is a useful means to enhance therapeutic vasculogenesis. (Lab Invest 2003, 83:65-73).

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Section: Discussionmentioning

confidence: 78%

Hypoxic Preconditioning Augments Efficacy of Human Endothelial Progenitor Cells for Therapeutic Neovascularization

Akita

Murohara

Ikeda

et al. 2003

Laboratory Investigation

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121

100

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“…In some animals, we saw an extensive infiltration of necrotic gastrocnemius muscle with T lymphocytes and dendritic cells, some of which were GFP + and hence donor in origin. Many preclinical studies have evaluated the benefits of mBMC transplantation in limb ischemia (5,43,44); however, in most studies, cells were injected only in the upper part of the limb, where inflammation due to necrosis is limited, which may have precluded the detection of the contribution of grafted immune cells to the inflammatory reaction. While we used unfractionated BMCs, in most clinical studies, only the mononuclear fraction or subsets of these are used (Supplemental Table 1).…”

Section: Discussionmentioning

confidence: 99%

Multipotent adult progenitor cells sustain function of ischemic limbs in mice

et al. 2008

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Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.

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“…(3,(6)(7)(8)(9) According to the literature, CLI complicates the course of eliminating atherosclerosis of the lower limbs in 33% of patients. (6,(10)(11)(12) As a result, the lethality and number of amputations now reaches 14.0% and 20.4%, respectively, in CLI patients after reconstructive interventions on the vascular bed. ( Reconstructive surgical interventions provide preservation of limbs in the postoperative period in terms up to 5 years in 80% of patients, up to 10 years -only in 50%.…”

Section: Introductionmentioning

confidence: 99%

Results of Surgical Treatment of Patients with Critical Limb Ischemia and Stenotic Lesions of the Brachiocephalic Arteries

Чарышкин¹,

Максин²,

Матвеева³

et al. 2017

IJBM

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The aim of our study was to evaluate the results of the surgical treatment for patients with critical limb ischemia (CLI) and stenotic lesions of the brachiocephalic arteries. Methods and Results:We examined 72 patients (68/87.2% men and 4/7.3% women) aged from 46 to 78 years (mean age, 62.2±4.3 years) with CLI and stenotic lesions of the brachiocephalic arteries. Conservative treatment was performed in 17(23.6%) patients and surgical treatment in 55(76.4%). It has been carried out 73 surgical operations: femoral popliteal bypass (5/6.8%), lumbar sympathectomy (4/5.5%), thrombectomy of occluded aortofemoral graft (2/2.7%), limb amputation (4/5.5%), iliofemoral bypass (4/5.5%), aortofemoral bifurcation bypass (10/13.1%), endovascular surgery (1/1.6%), limb amputation at thigh level -4(5.5%), thrombectomy of occluded distal arteries (4/5.5%), femoro-femoral cross-over bypass (1/1.6%), resection of popliteal artery aneurysm and prosthesis of the popliteal artery (1/1.6%), semi-closed loop endarterectomy of occluded arteries of the lower limbs (8/10.9%), carotid endarterectomy (23/31.5%), and carotid-subclavian bypass (2/2.7%). After the surgical intervention, we observed the disappearance or reduction of pain, restoration of sensitivity and motor activity, and healing of trophic ulcers in 75% of patients. In the late postoperative period, we detected the progression of limb ischemia in 4(5.5%) patients; in connection with that, we performed limb amputation at thigh level. Ischemic stroke with a lethal outcome developed in one patient (1.4%).Conclusion: In patients with multifocal atherosclerosis, multilevel reconstructive surgical interventions must be performed in stages, due to the high operational risk, and risk of complications, secondary amputations and lethality in the postoperative period.

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Augmentation of Postnatal Neovascularization With Autologous Bone Marrow Transplantation

Cited by 431 publications

References 41 publications

Hypoxic Preconditioning Augments Efficacy of Human Endothelial Progenitor Cells for Therapeutic Neovascularization

Hypoxic Preconditioning Augments Efficacy of Human Endothelial Progenitor Cells for Therapeutic Neovascularization

Multipotent adult progenitor cells sustain function of ischemic limbs in mice

Results of Surgical Treatment of Patients with Critical Limb Ischemia and Stenotic Lesions of the Brachiocephalic Arteries

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