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Persistence of unmet therapeutic needs in patients with Crohn's disease with luminal or perianal refractory disease has fostered the interest in innovative cellular immunoregulatory and regenerative medicines. Apart from autologous haematopoietic stem cell transplant, in which efficacy has been suggested in small series of patients and is now being evaluated in controlled trials, various groups have undertaken initiatives to determine the potential of mesenchymal stromal cell (MSC)-based therapy in Crohn's disease.
Bone marrow MSCs were first identified by Friedenstein, who described an adherent fibroblast-like population able to differentiate into bone. He referred to these cells as osteogenic precursor cells.1 Subsequent studies demonstrated that these cells have the ability to differentiate into various other mesodermal cell lineages, including chondrocytes, tenocytes and myoblasts. Based on this multilineage differentiation capacity, the term ‘mesenchymal stem cells’ was introduced.2 Although MSCs at a population level fulfil stem-cell criteria (ie, self-renewal and the capacity for multi-lineage differentiation), it remains questionable whether the qualification ‘stem cell’ is legitimate for MSCs at the single-cell level. It was therefore recently proposed that the term ‘multipotent mesenchymal stromal cells’ (with the abbreviation MSCs) should be used to describe fibroblast-like plastic-adherent cells.3
Although, originally, MSCs were isolated from bone marrow, similar populations have been isolated from other tissues, including adipose tissue, placenta, amniotic fluid and fetal tissues such as fetal lung and blood.2 To date, the isolation of MSCs still relies on their adherence to plastic, resulting in a heterogeneous population of adherent cells. No specific marker or combination of markers has been identified that specifically defines MSCs. Phenotypically, ex vivo expanded MSCs express a number of non-specific markers, including CD105 (SH2 or endoglin), CD73 (SH3 or SH4), CD90, CD166, CD44, and CD29, and are devoid …