Beneficial effects of autologous bone marrow cell infusion and antioxidants/L-arginine in patients with chronic critical limb ischemia.
BACKGROUND
Short-term (within 6 weeks follow-up) clinical studies indicate that implantation of bone marrow cells (BMCs) into ischemic limbs may improve peripheral ischemia. Here, the long-term safety and feasibility of intraarterial autologous BMCs with oral treatment with antioxidants and L-arginine were investigated in patients with critical ischemia on account of advanced atherosclerotic peripheral arterial disease (PAD).


METHODS
Eighteen patients with PAD (advanced III/IV Fontaine stages) were enrolled in this study (NCT00306085). An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control. The BMC-treated group received two doses of BMCs in the leg arteries (time 0 and 45 days). After 30 days from the first BMC dose, patients received daily antioxidants, and L-arginine. Therapeutic neoangiogenesis was estimated by angiography and laser Doppler\capillaroscopy.


RESULTS
Ankle brachial index improvement (DeltaABI: >0.1) was seen in 10 patients at 3 months and in 12 patients at 12-18 months. Ischemic ulcers improved in 13 patients (after 6-12 months). Although two patients underwent amputation, the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months. Among conservative patients, 10 underwent amputation in comparison with two BMC-treated patients (55.6 vs. 13.3%; P=0.014).


CONCLUSIONS
This small study shows that intraarterial autologous BMC and antioxidants and L-arginine therapy is safe and effective in patients with advanced atherosclerotic PAD with positive effects until 18 months.
Napoli
Claudio
C
Division of Clinical Pathology, Department of General Pathology, 1st School of Medicine, II University of Naples, Naples, Italy. claudio.napoli@unina2.it/claunap@tin.it
Farzati
Bartolomeo
B
Sica
Vincenzo
V
Iannuzzi
Emanuele
E
Coppola
Giuseppe
G
Silvestroni
Andrea
A
Balestrieri
Maria Luisa
ML
Florio
Anna
A
Matarazzo
Angelo
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D000842:Ankle / Q000098:blood supply; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D001794:Blood Pressure / Q000187:drug effects; D016026:Bone Marrow Transplantation; D001916:Brachial Artery / Q000503:physiopathology; D002908:Chronic Disease; D003131:Combined Modality Therapy; D016638:Critical Illness; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017078:Laser-Doppler Flowmetry; D007871:Leg Ulcer / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D020678:Microscopic Angioscopy; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D020127:Recovery of Function; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D016138:Walking
D000975:Antioxidants; D001120:Arginine