[Autologous bone marrow-derived stem cell therapy in patients with severe peripheral arterial disorder].
OBJECTIVE
Amputation is the only current option for relief of rest pain or gangrene in patients with severe peripheral arterial disease. Up to now, no effective blood-flow enhancement therapies are available. Autologous bone marrow-derived stem cell transplantation is an arising therapy modality with an option of building new blood vessels through endothelial stem and/or progenitor cells.


METHODS
Five patients with severe peripheral arterial disorder were treated by autologous bone marrow-derived stem cell therapy. CD34+, CD133+ and CD45+/- cell number and ratio were determined. CD34+ cells were isolated by magnetic separation and collected into a 10 ml sample. The cell suspension was administered by local intramuscular injections (0.5-1.0 ml injections in the musculus gastrocnemius). The follow-up (before; 1, 3, 6, 9 and 12 months after the autologous bone marrow-derived stem cell therapy) based on clinical (rest pain, walking distance without pain, changes of non-healing ischaemic ulcers, ankle-brachial index) and laboratory (angiography, Color- and Laser-Doppler scan, measurement of transcutaneous oxygen tension and endothelial function test) parameters was documented and analyzed.


RESULTS
Improvement of pain and walking distance was observed in all five cases. In three cases the non-healing ischaemic ulcers disappeared, in one other case they became smaller and thinner, and in one case no change was realized. The average of ankle-brachial index improved significantly (before: 0.41, twelve months after: 0.83). New collaterals were detected by angiography in three patients, but duplex ultrasonography detected improvement in one patient only. Before and 1, 6 and 12 months after stem cell therapy the transcutaneous oxygen tension changed on the foot from 18.80/16.78/23.83/37.50 mmHg, and on the calf from 36.66/31.25/45.00/37.30 mmHg. The macro- and microcirculation parameters did not show improvement after 1 month, however, after 3, 6, 9 and 12 months improved parameters were recorded. Severe adverse events were not observed. In one case elevated level of serum creatinine phosphokinase, and in another case a mild form of vasculitis were detected.


CONCLUSIONS
autologous bone marrow-derived stem cell therapy with isolated CD34+ cells is effective, safe and results in sustained clinical benefit for patients with severe peripheral arterial disease.
Boda
Zoltán
Z
Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Altalános Orvostudományi Kar II. Belgyógyászati Klinika, Haemostasis Tanszék Debrecen Nagyerdei krt. 98. 4012. zboda@dote.hu
Udvardy
Miklós
M
Farkas
Katalin
K
Tóth
Judit
J
Jámbor
László
L
Soltész
Pál
P
Rázsó
Katalin
K
Oláh
Zsolt
Z
Ilonczai
Péter
P
Szarvas
Mariann
M
Litauszky
Krisztina
K
Hunyadi
János
J
Sipos
Tamás
T
Kappelmayer
János
J
Veréb
Zoltán
Z
Rajnavölgyi
Eva
E
D000328:Adult; D000792:Angiography; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D016026:Bone Marrow Transplantation; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D007866:Leg / Q000098:blood supply* / Q000601:surgery; D007871:Leg Ulcer / Q000209:etiology / Q000601:surgery; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D012146:Rest; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation; D013997:Time Factors; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler; D016138:Walking
D018952:Antigens, CD34; D015415:Biomarkers; D017493:Leukocyte Common Antigens