Autologous progenitor cell implantation as a novel therapeutic intervention for ischaemic digits in systemic sclerosis.
OBJECTIVE
The effects of local stem cell implantation on clinical and functional characteristics of peripheral vascular disease were studied in two SSc patients with non-healing ischaemic ulcers.


METHODS
The local injections of CD34(+) cells from peripheral blood (PB) after mobilization by G-CSF (Case 1) and bone marrow (BM) (Case 2) were used for ischaemic skin ulcers in hands, while mononuclear cells (MNCs) were implanted in lower extremities of the same patients. Ischaemic status was evaluated by measuring ulcer healing, Raynaud's condition score (RCS), visual analogue pain, RP and ulcer scales. To evaluate vasculoprotective action of the implanted cells, we studied weekly the changes in endothelial function, using measurement of flow-mediated brachial artery reactivity by high-resolution ultrasonography, circulating endothelial precursors (CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) CEP) by FACS analysis, cutaneous blood flow (laser Doppler flowmetry), skin surface temperature (thermograph), peripheral arterial diameter and blood flow characteristics by Duplex ultrasonography.


RESULTS
CD34(+) cells and MNCs both from BM and PB showed rapid and evident beneficial effect on vascular symptoms resulting in ulcer healing, remarkably decreased daily frequency and duration of RP attacks, RCS, visual analogue scale for RP, ulcers and pain. Physical function and disability measured with HAQ and SHAQ improved. Therapeutic efficacy of stem cell therapy was associated with restoration of endothelial function, augmentation of microcirculatory blood flow and significant increase in circulating CD133(+)VEGFR2(+) progenitors, known as cell effectors of angiogenesis.


CONCLUSIONS
This first open-label pilot study demonstrates the feasibility and short-term safety of local CD34(+) cell therapy for SSc ischaemic complications.
Nevskaya
T
T
Department of Microcirculation and Inflammation, State Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow, Russia. tatiananevsk@mail.ru
Ananieva
L
L
Bykovskaia
S
S
Eremin
I
I
Karandashov
E
E
Khrennikov
J
J
Mach
E
E
Zaprjagaeva
M
M
Guseva
N
N
Nassonov
E
E
D000328:Adult; D018952:Antigens, CD34 / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D005385:Fingers / Q000098:blood supply* / Q000473:pathology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000628:therapy*; D008833:Microcirculation; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012595:Scleroderma, Systemic / Q000150:complications / Q000473:pathology / Q000628:therapy*; D012720:Severity of Illness Index; D012867:Skin / Q000098:blood supply; D012883:Skin Ulcer / Q000209:etiology / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
D018952:Antigens, CD34