Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents

Waters, Richard E.; Terjung, Ronald L.; Peters, Kevin G.; Annex, Brian H.

doi:10.1152/japplphysiol.00107.2004

Cited by 105 publications

(111 citation statements)

References 63 publications

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“…First, we compared the potential of mMAPC-U, mMAPC-VP, and mBMCs injected on the left side, immediately after femoral artery ligation in C57BL/6 mice, a model of moderate limb ischemia, reminiscent of IC in humans (25). Both sides were ligated (except in laser Doppler studies, where only the left side was ligated), which allowed evaluation of a possible contralateral effect of the graft.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, we tested the potential of mMAPC-U, mMAPC-U2 (2 independently derived clones), and hMAPC-U, transplanted 5 days after femoral or iliac ligation/transection in BALB/c-nu/nu mice, a model of severe limb ischemia, representative of CLI (25), as evidenced by the increased tissue necrosis rate (Table 1 versus Table 2). mMAPC-U, mMAPC-U2, and hMAPC-U grafting significantly expanded the collateral bed (2- to 3-fold increase in α-SMA + area), compared with control treatment (Figure 6, A-D and K, and Table 2) at 21 days.…”

Section: Differential Effects Of Mmapc-u Mmapc-vp and Mbmcs In Modementioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Differential Effects Of Mmapc-u Mmapc-vp and Mbmcs In Modementioning

confidence: 99%

Multipotent adult progenitor cells sustain function of ischemic limbs in mice

et al. 2008

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“…Several animal studies have addressed this question. They have been clear indications that ischaemia caused or aggravated by diabetes have been improved by stem cells [21,22].…”

Section: Stem Cell Treatment In Critical Limb Ischaemiamentioning

confidence: 99%

Stem cell therapy for critical limb ischaemia — a review

Das

2009

Indian J Surg

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Critical limb ischaemia is an intractable condition associated with high levels of amputation, leading to a low quality of life and increased morbidity and mortality. It is often not treatable by standard therapeutic modalities. Neoangiogenesis has been proposed as a novel method of treatment of such patients. Vascular endothelial growth factor (VEGF) and cytokine fi broblast growth factor (FGF-1) have been shown to elicit neoangiogenesis. Stem cells are progenitor cells which can differentiate in vivo into different types of cells. Mesenchymal stem cells (MSCs) are a type of adult stem cells which have an immunomodulatory effect. Stem cell therapy has been used in animal studies to improve limb vascularity in rat and rabbit models. Several clinical studies have also validated their use for critical limb ischaemia. However many issues are still unresolved. These include the dosage, delivery and safety issues in relation to stem cell therapy. However stem cells are likely to be an important therapeutic modality to treat critical limb ischaemia in the near future.

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“…PAD affects 15% of adults over 55; patients have a 25% higher mortality rate, and amputation is often performed (50,000 cases/year in the United States). 10,65 Exercise training is currently regarded as the most effective treatment for intermittent claudication. However, its therapeutic mechanisms are poorly understood and it is applied only to select patients.…”

Section: Introductionmentioning

confidence: 99%