Autologous Bone-Marrow Mononuclear Cell Implantation Improves Endothelium-Dependent Vasodilation in Patients With Limb Ischemia

Abstract

Background-Patients with limb ischemia were associated with endothelial dysfunction. The purpose of this study was to determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial dysfunction in patients with limb ischemia. Methods and Results-We evaluated the leg blood flow (LBF) response to acetylcholine (ACh), an endotheliumdependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after BM-MNC implantation in 7 patients with limb ischemia. LBF was measured with a mercury-filled Silastic strain-gauge plethysmograph. The number of BM-MNCs implanted into ischemic limbs was 1.6ϫ10 9 Ϯ0.3ϫ10 9 . The number of CD34 ϩ cells included in the implanted BM-MNCs was 3.8ϫ10 7 Ϯ1.6ϫ10 7 . BM-MNC implantation improved the ankle-brachial pressure index (0.33Ϯ0.21 to 0.39Ϯ0.17, Pϭ0.06), transcutaneous oxygen pressure (28.4Ϯ11.5 to 36.6Ϯ5.2 mm Hg, Pϭ0.03), and pain-free walking time (0.8Ϯ0.6 to 2.9Ϯ2.2 minutes, Pϭ0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3Ϯ6.8 versus 29.6Ϯ7.1 mL/min per 100 mL; Pϭ0.002). The vasodilatory effect of SNP was similar before and after BM-MNC implantation. Conclusions-These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.

Endothelial progenitor cells: Implications for cardiovascular disease

“…These results remained stable until the 24-week follow-up. Two other studies, using a similar approach in seven and eight patients with CLI, confirmed the safety and feasibility of intramuscular BM-MNC transplantation in PAOD (128,129). Moreover, Higashi et al assessed an improvement in endothelium-dependent vasodilatation after BM-MNC implantation in these patients with limb ischemia.…”

Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long-term prognosis

“…21 Although BMMNC or M-PBMNC intramuscular implantation has been used most often, both therapies have some risk: to collect about 500 mL of BMMNC, general anesthesia of about 4 h duration is necessary, and to collect PBMNC, about 3 h of apheresis with G-CSF treatment is required. [2][3][4][5][6][7][8][9][10][11][14][15][16][17][18] In a first cell-therapy trial, results of which were published in 2002, 22 ASO patients (44 limbs) were implanted with either BMMNC or PBMNC. 2 At 6 months after implantation, both therapies yielded improvements in terms of rest pain, ABI and transcutaneous oxygen pressure, but the clinical outcomes for BMMNC were significantly better than those for PBMNC.…”

A terapia celular no tratamento da isquemia crítica dos membros inferiores

“…Outra possibilidade é a de que as próprias CTA produziriam esses fatores de estímulo, que concorreriam para a formação de novos vasos, inclusive estimulando CP "residentes" na região isquêmica (atividade paracrina) [40][41][42] , e ainda concorreriam para a melhora do funcionamento do endotélio dos vasos remanescentes, além de promover a sua vasodilação 43 . É provável que haja uma associação desses vários mecanismos para que haja vasculogênese.…”

“…Higashi et al 43 demonstraram que o implante de células mononucleares de medula óssea melhorava a vasodilatação dependente do endotélio em pacientes com isquemia de membros inferiores, isto é, melhorava o desempenho do endotélio dos vasos remanescentes.…”