title: Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing.
abstract: The effect of cryopreservation on mesenchymal stromal cell (MSC) therapeutic properties has become highly controversial. However, data thus far have indiscriminately involved the assessment of different types of MSCs with distinct production processes. This study assumed that MSC-based products are affected differently depending on the tissue source and manufacturing process and analyzed the effect of cryopreservation on a specific population of umbilical cord tissue-derived MSCs (UC-MSCs), UCX®.
  
  
  
  Cell phenotype was assessed by flow cytometry through the evaluation of the expression of relevant surface markers such as CD14, CD19, CD31, CD34, CD44, CD45, CD90, CD105, CD146, CD200, CD273, CD274 and HLA-DR. Immunomodulatory activity was analyzed in vitro through the ability to inhibit activated T cells and in vivo by the ability to reverse the signs of inflammation in an adjuvant-induced arthritis (AIA) model. Angiogenic potential was evaluated in vitro using a human umbilical vein endothelial cell-based angiogenesis assay, and in vivo using a mouse model for hindlimb ischemia.
  
  
  
  Phenotype and immunomodulatory and angiogenic potencies of this specific UC-MSC population were not impaired by cryopreservation and subsequent thawing, both in vitro and in vivo.
  
  
  
  This study suggests that potency impairment related to cryopreservation in a given tissue source can be avoided by the production process. The results have positive implications for the development of advanced-therapy medicinal products.
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal.
authors.forename: Rita N
authors.initials: RN
authors.lastname: Bárcia
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Santos
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Teixeira
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Filipe
authors.affiliation: Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Ana Rita S
authors.initials: ARS
authors.lastname: Pereira
authors.affiliation: Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal; Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
authors.forename: Augusto
authors.initials: A
authors.lastname: Ministro
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Água-Doce
authors.affiliation: iMed.Ulisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Carvalheiro
authors.affiliation: iMed.Ulisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
authors.forename: Maria Manuela
authors.initials: MM
authors.lastname: Gaspar
authors.affiliation: iMed.Ulisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
authors.forename: Joana P
authors.initials: JP
authors.lastname: Miranda
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Graça
authors.affiliation: iMed.Ulisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Simões
authors.affiliation: Centro Cardiovascular da Universidade de Lisboa, Lisboa, Portugal; Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Susana Constantino Rosa
authors.initials: SCR
authors.lastname: Santos
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.affiliation: ECBio, Investigação e Desenvolvimento em Biotecnologia, S.A., Amadora, Portugal. Electronic address: helder.cruz@ecbio.com.
authors.forename: Helder
authors.initials: H
authors.lastname: Cruz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D015925:Cryopreservation; D005260:Female; D005434:Flow Cytometry; D005615:Freezing / Q000009:adverse effects; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D014470:Umbilical Cord / Q000166:cytology*
keywords: advanced-therapy medicinal product; cryopreservation; mesenchymal stromal cells; potency; thawing