Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells

Motukuru, Vishnu; Suresh, Kalkunte R; Vivekanand, Vivekanand; Raj, Satish R.; Girija, KR

doi:10.1016/j.jvs.2008.09.005

Cited by 72 publications

(57 citation statements)

References 25 publications

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“…The utility of BM derived mononuclear cells to produce angiogenesis in 33 Indian patients with Buerger's disease was evaluated, where major amputation was done for 3 patients (12 %). The mean ABI improvement after 6 months in the salvaged limbs was 0.14 (Motukuru et al 2008). A similar study investigated BM-mononuclear cell transplantation in 7 patients with critical lower limb ischemia (3 with Buerger's disease, 4 with arteriosclerosis obliterans undergoing chronic hemodialysis).…”

Section: Discussionmentioning

confidence: 98%

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

et al. 2014

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Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia.

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Section: Discussionmentioning

confidence: 98%

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

et al. 2014

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“…In a preliminary safety and efficacy study by Motukuru et al [17], autologous bone marrow mononuclear cells injected into calf muscles of patients with BD resulted in effective ulcer healing, increased ABI, and improved transcutaneous oximetry, with limb salvage till 6 months in 33 of 36 patients. A review of total 18 clinical studies in English literature overviews the demonstrated safety and promising efficacy of autologous stem cells therapy for BD [18].…”

Section: Discussionmentioning

confidence: 99%

“…Stem cells are novel therapy stimulating neoangiogenesis to improve circulation in the ischemic limbs. Therapeutic angiogenesis with stem cells, although potentially promising for treatment of BD, is still at an early stage and limited to clinical trials [16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Although this study encompassed a small cohort of 20 patients, none of the patients developed recurrence during follow-up of 1-5 years (mean 3. A few authors have described improvement in microcirculation after treatment of CLI, as measured by DSA [17], Doppler [27,28], plethysmography [29], thallium scintigraphy, or RBC scan. In this preliminary study, CTA, a noninvasive imaging tool, has been used for assessment of vascular changes, with efficacy for vascular imaging, similar to DSA.…”

Section: Discussionmentioning

confidence: 99%

“…Angiogenic stem cell therapy is potentially promising, but is not suitable or immediately effective for relief of agonizing rest pain of critical limb ischemia (CLI) [16][17][18][19][20]. Anticoagulants, thrombolytic and antiplatelet drugs have shown favorable results for treatment of BD in some studies [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Improvement in Blood Supply After “Heparin-Dextran” Therapy in Patients of Buerger’s Disease with Critical Limb Ischemia

et al. 2012

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Alleviating the agonizing pain of critical limb ischemia (CLI) in patients of Buerger's disease (BD) has been challenging, due to lack of definitive treatment; "Heparin-Dextran" infusion has been tried in this study. Assessment of clinical improvement and vascular changes following therapy. Patients with CLI admitted to emergency surgical ward were studied prospectively. BD was diagnosed by Shionoya's criteria, and confirmed by digital subtraction angiography (DSA). Heparin and Dextran intravenous infusion was administered for 10 days. Severity of rest pain, ischemic changes in the feet, claudication distance and ankle brachial index (ABI) were estimated prior to therapy, at completion and 3 weeks after therapy. Vascular changes were assessed by CT angiography (CTA) performed prior to and 3 weeks after therapy. Twenty consecutive patients were studied. Successful hemodilution reflected by decreased hematocrit (37.4 % to 32.6 %, p<0.05) and increased mean ABI (0.46 to 0.83, p<0.01), improved rest pain in 75 % patients (p<0.001), increased claudication distance in 94 % (p<0.05) and ulcers healing in 70 % patients. CTA revealed recanalised vessels (decreased length of occluded segments) in 10 (50 %, p00.005), increased collaterals in 12 (60 %, p<0.01) and improved distal run-off in 13 (65 %, p<0.01) patients. "Heparin-Dextran" therapy in patients of CLI from BD improves tissue perfusion by increasing collaterals and recanalisation of vessels, resulting in significant relief from rest pain and clinical improvements. CTA is as efficacious as DSA for evaluation of BD.

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Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients

Fadilah

Ismail

Jamaludin

et al. 2018

Cochrane Database of Systematic Reviews

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Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.

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Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells

Cited by 72 publications

References 25 publications

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

Improvement in Blood Supply After “Heparin-Dextran” Therapy in Patients of Buerger’s Disease with Critical Limb Ischemia

Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients

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