Finessing the manufacture of mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSCs) are an appealing cellular therapy, with early-phase clinical studies underway as therapies for acute graft-versus-host disease, inflammatory bowel disease, diabetes, wound repair and other diseases. The relative ease with which these cells can be expanded makes them especially appealing. With the use of a bone marrow aspirate, tissue culture flasks and a simple medium, MSCs can be expanded by most laboratories. One concern, however, is the type of growth factor used in the medium. The use of growth factors in cell therapy products—in particular, MSCs—is an important consideration when validating the expansion of these products for clinical use ( 1 Philippe B. Luc S. Valerie P.B. Jerome R. Alessandra B.R. Louis C. Culture and use of mesenchymal stromal cells in phase I and II clinical trials. Stem Cells Int. 2010; 2010: 503593 Crossref PubMed Scopus (53) Google Scholar , 2 Hanley P.J. Mei Z. da Graca Cabreira-Hansen M. Klis M. Li W. Zhao Y. et al. Manufacturing mesenchymal stromal cells for phase I clinical trials. Cytotherapy. 2013; 15: 416-422 Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar ). Foregoing fetal bovine serum (FBS) in favor of human platelet lysate has been reported to promote better expansion ( 3 Bieback K. Platelet lysate as replacement for fetal bovine serum in mesenchymal stromal cell cultures. Transfus Med Hemother. 2013; 40: 326-335 Crossref PubMed Scopus (142) Google Scholar ) and function of MSCs, and, unlike FBS, has not been shown to elicit immunological responses in recipients ( 4 Horwitz E.M. Gordon P.L. Koo W.K. Marx J.C. Neel M.D. McNall R.Y. et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci U S A. 2002; 99: 8932-8937 Crossref PubMed Scopus (1415) Google Scholar , 5 Sundin M. Ringden O. Sundberg B. Nava S. Gotherstrom C. Le Blanc K. No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica. 2007; 92: 1208-1215 Crossref PubMed Scopus (248) Google Scholar ) Nevertheless, the use of platelet lysate (and FBS) is not without risk because platelet lysate has the potential to transfer adventitious agents to the recipient.