Phenotypical and functional characteristics of in vitro expanded bone marrow mesenchymal stem cells from systemic sclerosis patients

Jérôme Larghero ¹, Dominique Farge ¹, Alessandra Braccini ², Séverine Lecourt ¹, Arnaud Scherberich ², Elena Foïs ¹, Franck Verrecchia ¹, Thomas Daikeler ³, Eliane Gluckman ¹, Alan Tyndall ³ and Chiara Bocelli-Tyndall ^3*

¹ Saint-Louis Hospital, France
² University Hospital Basel, Switzerland
³ University of Basel, Switzerland

^* To whom correspondence should be addressed. E-mail: chiara.tyndall{at}fps-basel.ch.

Accepted 18 May 2007

Abstract

Background: Mesenchymal stem cells (MSCs) have a potential immunomodulatory role in autoimmune disease (AD), but the qualitative properties and hematopoietic support capacity of MSCs derived from AD patients is unclear.

Objectives: To further characterise phenotypically and functionally bone marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc). Methods: Key parameters of BM derived MSC function and phenotype were assessed in 12 SSc patients and compared to 13 healthy normal controls. The parameters included the ability: to form colony forming unit-fibroblast (CFU-F), to differentiate along the adipogenic and osteogenic lineages, to express cell surface antigens defining the MSCs population, to support normal hematopoiesis and to suppress in vitro lymphocyte proliferation induced by either anti-CD3 plus anti-CD28 monoclonal antibodies or the mixed lymphocyte reaction.

Results: SSc MSCs were shown to have similar characteristic phenotype, capacities to form CFU-F and to differentiate along adipogenic and osteogenic lineages as those of healthy donor MSCs. The ability of SSc MSCs to support long-term hematopoiesis was also identical to that of controls. Both healthy donor and SSc patient BM-MSCs reduced the proliferation of autologous and allogeneic PBMCs in a cell number dependent fashion.

Conclusion: These results show that BM-derived MSCs from SSc patients under the described culture conditions exhibit the same phenotypic, proliferative, differentiation potential and immunosuppressive properties as their healthy counterparts and could therefore be considered in an autologous setting. Further studies are needed to ensure quality and safety of large scale expansion of patient MSCs prior to their potential use in clinical trials.

Keywords: autoimmune disease, hematopoiesis, immune response regulation, mesenchymal stem cells, systemic sclerosis

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