PMID- 31196185 OWN - NLM STAT- MEDLINE DCOM- 20200629 LR - 20200629 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 10 IP - 1 DP - 2019 Jun 13 TI - HLA-DR expression in clinical-grade bone marrow-derived multipotent mesenchymal stromal cells: a two-site study. PG - 164 LID - 10.1186/s13287-019-1279-9 [doi] LID - 164 AB - BACKGROUND: Contrary to the minimal criteria proposed by the International Society for Cell and Gene Therapy for defining multipotent mesenchymal stromal cells (MSC), human leukocyte antigen (HLA)-DR expression is largely unpredictable in ex vivo-expanded clinical-grade cultures. Although activation of MSC in culture does not appear to affect their functionality, a large study investigating the impact of HLA-DR expression on cell identity and potency is still missing in the literature. METHODS: A retrospective analysis of HLA-DR expression in 130 clinical batches of bone marrow (BM)-MSC from two independent Good Manufacturing Practice-compliant production facilities was performed in order to identify the consequences on critical quality attributes as well as potential activation cues and dynamics of MSC activation in culture. RESULTS: HLA-DR(+) cells in culture were confirmed to maintain fibroblastic morphology, mesenchymal phenotype identity, multipotency in vitro, and immunomodulatory capacity. Interestingly, the use of either human sera or platelet lysate supplements resulted in similar results. CONCLUSIONS: HLA-DR expression should be considered informative rather than as a criterion to define MSC. Further work is still required to understand the impact of HLA-DR expression in the context of product specifications on BM-MSC qualities for clinical use in specific indications. FAU - Grau-Vorster, Marta AU - Grau-Vorster M AD - Servei de Terapia Cel.lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jorda, Passeig Taulat, 116, 08005, Barcelona, Spain. AD - Transfusion Medicine Group, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035, Barcelona, Spain. FAU - Laitinen, Anita AU - Laitinen A AD - Finnish Red Cross Blood Service, Advanced Cell Therapy Centre, Kivihaantie 7, FIN-00310, Helsinki, Finland. FAU - Nystedt, Johanna AU - Nystedt J AD - Finnish Red Cross Blood Service, Advanced Cell Therapy Centre, Kivihaantie 7, FIN-00310, Helsinki, Finland. johanna.nystedt@gmail.com. FAU - Vives, Joaquim AU - Vives J AUID- ORCID: 0000-0001-9719-5235 AD - Servei de Terapia Cel.lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jorda, Passeig Taulat, 116, 08005, Barcelona, Spain. jvives@bst.cat. AD - Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035, Barcelona, Spain. jvives@bst.cat. AD - Departament de Medicina, Universitat Autonoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035, Barcelona, Spain. jvives@bst.cat. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190613 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (HLA-DR Antigens) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Apoptosis/drug effects/physiology MH - Bone Marrow Cells/drug effects/*metabolism MH - Cell Differentiation/drug effects/physiology MH - Cell Survival/drug effects/physiology MH - Cell- and Tissue-Based Therapy MH - Cells, Cultured MH - HLA-DR Antigens/*metabolism MH - Humans MH - Interferon-gamma/pharmacology MH - Mesenchymal Stem Cells/drug effects/metabolism MH - Retrospective Studies PMC - PMC6567533 OTO - NOTNLM OT - Cell culture OT - Cellular therapy OT - HLA-DR OT - Identity OT - Multipotent mesenchymal stromal cell OT - Potency OT - Quality compliance COIS- The authors declare that they have no competing interests. EDAT- 2019/06/15 06:00 MHDA- 2020/07/01 06:00 PMCR- 2019/06/13 CRDT- 2019/06/15 06:00 PHST- 2019/04/05 00:00 [received] PHST- 2019/05/23 00:00 [accepted] PHST- 2019/05/13 00:00 [revised] PHST- 2019/06/15 06:00 [entrez] PHST- 2019/06/15 06:00 [pubmed] PHST- 2020/07/01 06:00 [medline] PHST- 2019/06/13 00:00 [pmc-release] AID - 10.1186/s13287-019-1279-9 [pii] AID - 1279 [pii] AID - 10.1186/s13287-019-1279-9 [doi] PST - epublish SO - Stem Cell Res Ther. 2019 Jun 13;10(1):164. doi: 10.1186/s13287-019-1279-9.