Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial.
BACKGROUND
Critical limb ischemia is a manifestation of peripheral arterial disease characterized by insufficient arterial blood flow for maintaining tissue viability in the lower extremities. Therapeutic angiogenesis is used for peripheral arterial disease patients who are not candidates for surgical revascularization or radiological intervention. There is accumulating evidence for the beneficial impact of autologous bone marrow mononuclear cell transplantation for treatment of critical limb ischemia in humans. This study aims to investigate the safety and efficacy of repeated bone marrow mononuclear cell injections in comparison with a single bone marrow mononuclear cell injection in critical limb ischemia patients.


METHODS
Patients with critical limb ischemia (n = 22) were randomized (http://clinicaltrials.gov/ct2 show/NCT01480414) to receive either a single (n = 11) or four (n = 11) intramuscular injections of bone marrow mononuclear cells as a cell therapy product.


RESULTS
There were no reported adverse events during the 24-week follow-up period after cell delivery. Efficacy assessment indicated that after cell injections, there was significant improvement in Ankle-Brachial Index, Visual Analog Scale, pain-free walking distance, and Wagner stage as well as reduction in ulcer size. There was no significant difference between the two groups in terms of clinical parameters. However, by the 24th week the pain-free walking distance improved significantly in the group who received four injections of cells.


CONCLUSIONS
Favorable clinical outcomes strongly indicate the long-term benefit of bone marrow mononuclear cell transplantation, either as one or several injections, for retrieval from critical limb ischemia. Repeated cell injections have shown increased improvement of pain-free walking distance in patients. These findings warrant further exploration in later-phase clinical trials with repeated injections.
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Behnam
B
Molavi
Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Reza
MR
Zafarghandi
Department of Vascular Surgery, Tehran University of Medical Sciences, Tehran, Iran.
Ehsan
E
Aminizadeh
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Seyyedeh-Esmat
SE
Hosseini
Department of Vascular Surgery, Tehran University of Medical Sciences, Tehran, Iran.
Hamid
H
Mirzayi
Department of Vascular Surgery, Tehran University of Medical Sciences, Tehran, Iran.
Leila
L
Arab
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Hossein
H
Baharvand
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Nasser
N
Aghdami
D000328:Adult; D000671:Amputation, Surgical; D016026:Bone Marrow Transplantation / Q000379:methods*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D058729:Peripheral Arterial Disease / Q000628:therapy*; D010865:Pilot Projects; D014182:Transplantation, Autologous / Q000379:methods; D016896:Treatment Outcome