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

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.

Circulating endothelial progenitor cells in systemic sclerosis: relation to impaired angiogenesis and cardiovascular manifestations.

OBJECTIVE: Given the essential role of endothelial progenitor cells (EPCs) in endothelial repair and neovascularization, it is likely that insufficient angiogenesis seen in systemic sclerosis (SSc) is related to EPC alterations. The present study was aimed to analyze in SSc the number of circulating EPCs and their contribution into cardiovascular involvement. METHODS: EPC (CD34+VEGF-R2+ and CD133+VEGF-R2+) circulating levels were evaluated in 40 SSc patients and 24 controls by FACS; their correlations with peripheral vascular manifestations, heart involvement, Framingham risk score, carotid artery disease, endothelial function and morphological signs of microangiopathy were studied. RESULTS: Early stage SSc and high disease activity were accompanied by a rise in circulating EPC levels in association with increased membrane expression of Fas (CD95) that correlated positively with severity of peripheral vascular manifestations. EPC reduction with disease progression was linked with endothelial dysfunction and capillary loss, and showed a strong relation to the development of severe internal organ (predominantly cardiac) involvement and pulmonary hypertension. There was a tendency to decreased EPC levels in SSc pts with low HDL values, but no significant correlations were found between EPCs and Framingham risk factor score, carotid artery IMT and traditional cardiovascular risk factors. CONCLUSIONS: In early stage SSc mobilization of EPCs in response to tissue ischemia was preserved, but dropped with disease progression. EPC reduction may contribute to endothelial dysfunction and impaired angiogenesis, leading to the development of severe vascular life-threatening complications of SSc. Traditional cardiovascular risk factors and subclinical atherosclerosis did not influence EPC levels in SSc patients.