title: A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance.
abstract: The inherent immunomodulatory capacity of mesenchymal stem/progenitor cells (MSPCs) encouraged initiation of multiple clinical trials. Release criteria for therapeutic MSPCs cover identity, purity and safety but appropriate potency assessment is often missing. Reports on functional heterogeneity of MSPCs created additional uncertainty regarding donor and organ/source selection. We established a robust immunomodulation potency assay based on pooling responder leukocytes to minimize individual immune response variability. Comparing various MSPCs revealed significant potency inconsistency and generally diminished allo-immunosuppression compared to dose-dependent inhibition of mitogenesis. Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies.
authors.affiliation: Experimental and Clinical Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. nina.ketterl@pmu.ac.at.
authors.forename: Nina
authors.initials: N
authors.lastname: Ketterl
authors.affiliation: Experimental and Clinical Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. gabriele.brachtl@pmu.ac.at.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Brachtl
authors.affiliation: Experimental and Clinical Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. cornelia.schuh@pmu.ac.at.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schuh
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany. karen.bieback@medma.uni-heidelberg.de.
authors.forename: Karen
authors.initials: K
authors.lastname: Bieback
authors.affiliation: Department of Transfusion Medicine and Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. k.schallmoser@salk.at.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schallmoser
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA, USA. reinisch@stanford.edu.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reinisch
authors.affiliation: Experimental and Clinical Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. dirk.strunk@pmu.ac.at.
authors.forename: Dirk
authors.initials: D
authors.lastname: Strunk
mesh_terms: D000328:Adult; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005720:Gamma Rays; D006801:Humans; D056747:Immunomodulation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D011836:Radiation Tolerance; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014019:Tissue Donors; D055815:Young Adult