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Rheumatology Advance Access published online on November 20, 2008
Rheumatology, doi:10.1093/rheumatology/ken407
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Autologous progenitor cell implantation as a novel therapeutic intervention for ischaemic digits in systemic sclerosis

T. Nevskaya1, L. Ananieva1, S. Bykovskaia2, I. Eremin2, E. Karandashov2, J. Khrennikov3, E. Mach4, M. Zaprjagaeva4, N. Guseva1 and E. Nassonov1

1Department of Microcirculation and Inflammation, 2Cell Monitoring Laboratory, 3Department of Traumatology and Orthopedics and 4Laboratory of Functional Diagnostics, State Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow, Russia.

Correspondence to: T. Nevskaya, Kashirskoe sh. 34a, 115522, Moscow, Russia. E-mail: tatiananevsk{at}mail.ru


  Abstract

Objectives. 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.

Conclusion. This first open-label pilot study demonstrates the feasibility and short-term safety of local CD34+ cell therapy for SSc ischaemic complications.

KEY WORDS: Stem cells, Endothelial progenitors, Therapy, Angiogenesis, Systemic sclerosis, Fingertip ulcers

Submitted 25 June 2008; revised version accepted 18 September 2008.
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