Autologous bone marrow cell implantation as therapeutic  angiogenesis for ischemic hindlimb in diabetic rat model

The angiogenic effect induced by autologous bone marrow cell implantation (BMCI) was examined in the ischemic hindlimbs of diabetic and nondiabetic rats. Diabetes mellitus was induced by the systemic administration of streptozotocin. We investigated the production of angiogenic factors and endothelial differentiation from bone marrow cells and the native recovery of blood flow in the ischemic hindlimbs. To observe the angiogenic effect induced by BMCI treatment, 6 × 107 bone marrow cells were injected intramuscularly at six points into the ischemic limbs, and regional perfusion recovery was evaluated with colored microspheres 2 wk later. No difference was found between diabetic and nondiabetic rats in the release of angiogenic factors or endothelial differentiation from bone marrow cells in vitro. The levels of nitric oxide in plasma were significantly lower, and native perfusion recovery in the ischemic hindlimbs was significantly slower in the diabetic rats than in the nondiabetic rats. However, although perfusion recovery was achieved in the ischemic hindlimbs, there was no significant increase in systemic VEGF after BMCI treatment in either the diabetic or nondiabetic rats. Therefore, therapeutic angiogenesis induced by BMCI could be a safe and effective treatment for ischemic limb disease in diabetic patients.

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Therapeutic angiogenesis by transplantation of autologous bone marrow cells.

SEIBUTSU BUTSURI KAGAKU ◽

10.2198/sbk.48.129 ◽

2004 ◽

Vol 48 (4) ◽

pp. 129-131

Author(s):

Uichi Ikeda

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Autologous Bone Marrow ◽

Therapeutic Angiogenesis ◽

Autologous Bone ◽

Marrow Cells

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Therapeutic Angiogenesis by Autologous Bone Marrow Cell Implantation for Refractory Chronic Peripheral Arterial Disease Using Assessment of Neovascularization by 99mTc-Tetrofosmin (TF) Perfusion Scintigraphy

Cell Transplantation ◽

10.3727/000000004783983837 ◽

2004 ◽

Vol 13 (4) ◽

pp. 429-438 ◽

Cited By ~ 83

Author(s):

Masaaki Miyamoto ◽

Masahiro Yasutake ◽

Hitoshi Takano ◽

Hiromichi Takagi ◽

Gen Takagi ◽

...

Keyword(s):

Bone Marrow ◽

Marrow Cell ◽

Autologous Bone Marrow ◽

Arterial Disease ◽

Therapeutic Angiogenesis ◽

Perfusion Scintigraphy ◽

99Mtc Tetrofosmin ◽

Autologous Bone ◽

Peripheral Arterial ◽

Cell Implantation

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Design and rationale of a randomized, double-blind, placebo-controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT-CLI)

VASA ◽

10.1024/0301-1526.37.4.319 ◽

2008 ◽

Vol 37 (4) ◽

pp. 319-325 ◽

Cited By ~ 23

Author(s):

Amann ◽

Lüdemann ◽

Rückert ◽

Lawall ◽

Liesenfeld ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cell ◽

Critical Limb Ischemia ◽

Bone Marrow Cells ◽

Marrow Cell ◽

Autologous Bone Marrow ◽

Limb Ischemia ◽

Major Amputation ◽

Autologous Bone ◽

Marrow Cells

Background: Critical limb ischemia (CLI) is the end-stage of peripheral artery disease. Only about two thirds of patients with CLI can be revascularised, one third progresses to leg amputation with high associated morbidity and mortality. Therapeutic angiogenesis with bone marrow cells has shown promising improvement in less severe stages of peripheral ischemia. Our study evaluates the therapeutic value of bone marrow cell induced angiogenesis and arteriogenesis in severe, limb-threatening ischemia. Patients and methods: the BONe Marrow Outcome Trial in Critical Limb Ischemia (BONMOT-CLI) is a investigator-initiated, double-blinded, 1:1 randomized, placebo-controlled multi-centre study at 4 sites in Germany. Only patients with no option for revascularisation or after failed revascularisation will be included. A total of 90 patients is to be included. One arm with 45 subjects will be treated with a concentrate of autologous bone marrow cells which will be injected at 40 sites into the ischemic limb. In the placebo arm, study subjects will undergo a sham bone marrow punction and 40 saline injections. At three months, a combined primary endpoint of major amputation or persisting critical limb ischemia (no clinical or perfusion improvement) will be evaluated. Secondary endpoints are death, changes in perfusion, quality of life, walking distance, minor amputations, wound healing, collateral density and cancer incidence. Post-study follow-up is up to two years. Conclusions: The results of this first randomized placebo-controlled trial for autologous bone marrow cell therapy in CLI will clarify the value of this new therapeutic modality in a patient population with no other alternatives except major amputation.

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