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BMJ Open. 2013 Jan 7;3(1). pii: e001890. doi: 10.1136/bmjopen-2012-001890.

Expression of transforming growth factor β receptor II in mesenchymal stem cells from systemic sclerosis patients.

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1
Unité de Thérapie Cellulaire et Centre d'Investigation Clinique en Biothérapies CIC-BT501, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France.

Abstract

OBJECTIVES:

The present work aimed to evaluate the expression of transforming growth factor-β (TGF-β) receptors on bone marrow-derived multipotent mesenchymal stromal cells (MSCs) in patients with systemic sclerosis (SSc) and the consequences of TGF-β activation in these cells, since MSC have potential therapeutic interest for SSc patients and knowing that TGF-β plays a critical role during the development of fibrosis in SSc.

DESIGN:

This is a prospective research study using MSC samples obtained from SSc patients and compared with MSC from healthy donors.

SETTING:

One medical hospital involving collaboration between an internal medicine department for initial patient recruitment, a clinical biotherapeutic unit for MSC preparation and an academic laboratory for research.

PARTICIPANTS:

9 patients with diffuse SSc for which bone marrow (BM) aspiration was prescribed by sternum aspiration before haematopoietic stem cell transplantation, versus nine healthy donors for normal BM.

PRIMARY AND SECONDARY OUTCOME MEASURES:

TGF-β, TGF-β receptor types I (TBRI) and II (TBRII) mRNA and protein expression were assessed by quantitative PCR and flow cytometry, respectively, in MSC from both SSc patients and healthy donors. MSC were exposed to TGF-β and assessed for collagen 1α2 synthesis and Smad expression. As positive controls, primary cultures of dermal fibroblasts were also analysed.

RESULTS:

Compared with nine controls, MSC from nine SSc patients showed significant increase in mRNA levels (p<0.002) and in membrane expression (p<0.0001) of TBRII. In response to TGF-β activation, a significant increase in collagen 1α synthesis (p<0.05) and Smad-3 phosphorylation was upregulated in SSc MSC. Similar results were obtained on eight SSc-derived dermal fibroblasts compared to six healthy controls.

CONCLUSIONS:

TBRII gene and protein expression defect in MSC derived from SSc patients may have pathological significance. These findings should be taken into account when considering the use of MSC-based therapies in an autologous setting.

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