title: Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media.
abstract: Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been evaluated for the treatment of immunological diseases. However, the animal-derived growth supplements utilized for MSC manufacturing may lead to clinical complications. Characterization of alternative media formulations is imperative for MSC therapeutic application. Human BMMSC and AdMSC were expanded in media supplemented with either human platelet lysates (HPL), serum-free media/xeno-free FDA-approved culture medium (SFM/XF), or fetal bovine serum (FBS) and the effects on their properties were investigated. The immunophenotype of resting and IFN-γ primed BMMSC and AdMSC remained unaltered in all media. Both HPL and SFM/XF increased the proliferation of BMMSC and AdMSC. Expansion of BMMSC and AdMSC in HPL increased their differentiation, compared to SFM/XF and FBS. Resting BMMSC and AdMSC, expanded in FBS or SFM/XF, demonstrated potent immunosuppressive properties in both non-primed and IFN-γ primed conditions, whereas HPL-expanded MSC exhibited diminished immunosuppressive properties. Finally, IFN-γ primed BMMSC and AdMSC expanded in SFM/XF and HPL expressed attenuated levels of IDO-1 compared to FBS. Herein, we provide strong evidence supporting the use of the FDA-approved SFM/XF medium, in contrast to the HPL medium, for the expansion of MSC towards therapeutic applications.
authors.affiliation: Center for Inflammatory Bowel Diseases, Melvin and Bren Simon Digestive Diseases Center, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Angelos
authors.initials: A
authors.lastname: Oikonomopoulos
authors.affiliation: Center for Inflammatory Bowel Diseases, Melvin and Bren Simon Digestive Diseases Center, David Geffen School of Medicine, UCLA, Los Angeles, California.|Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Welmoed K
authors.initials: WK
authors.lastname: van Deen
authors.affiliation: Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Aida-Rae
authors.initials: AR
authors.lastname: Manansala
authors.affiliation: Center for Inflammatory Bowel Diseases, Melvin and Bren Simon Digestive Diseases Center, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Precious N
authors.initials: PN
authors.lastname: Lacey
authors.affiliation: Center for Inflammatory Bowel Diseases, Melvin and Bren Simon Digestive Diseases Center, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Tamera A
authors.initials: TA
authors.lastname: Tomakili
authors.affiliation: Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Ziman
authors.affiliation: Center for Inflammatory Bowel Diseases, Melvin and Bren Simon Digestive Diseases Center, David Geffen School of Medicine, UCLA, Los Angeles, California.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D052242:Adiponectin / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002457:Cell Extracts / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005312:Fetal Blood / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry
chemical_list: D052242:Adiponectin; D002457:Cell Extracts; D003470:Culture Media; D016895:Culture Media, Serum-Free; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D047495:PPAR gamma; D007371:Interferon-gamma; D000469:Alkaline Phosphatase