Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial.
Stem Cells
; 27(11): 2857-64, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19711453
ABSTRACT
A number of preclinical studies have indicated the therapeutic potential of endothelial progenitor cells for vascular regeneration in ischemic diseases. A phase I/IIa clinical trial of transplantation of autologous CD34(+) cells, the endothelial and hematopoietic progenitor-enriched fraction, was performed in no-option patients with atherosclerotic peripheral artery disease or Buerger's disease with critical limb ischemia (CLI). CD34(+) cells were isolated from the G-CSF-mobilized apheresis product using a magnetic cell sorting system. CD34(+) cells (10(5)/kg, n = 6; 5 x 10(5)/kg, n = 8; or 10(6)/kg, n = 3) were injected i.m. into the leg with more severe ischemia. The Efficacy Score, representing changes in the toe brachial pressure index (TBPI), Wong-Baker FACES pain rating scale, and total walking distance 12 weeks after cell transplantation, the primary endpoint, was positive, indicating improvement in limb ischemia in all patients, although no significant dose-response relationship was observed. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, TBPI, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients. No death or major amputation occurred, and severe adverse events were rare, although mild to moderate events relating to G-CSF and leukapheresis were frequent during the 12-week follow-up. In conclusion, the outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with CLI. Favorable trends in efficacy parameters encourage a randomized and controlled trial in the future.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Fator Estimulador de Colônias de Granulócitos
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Antígenos CD34
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Terapia Baseada em Transplante de Células e Tecidos
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Isquemia
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Perna (Membro)
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
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Aged80
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão