Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing

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• 作者：Rita N. Bá ; rcia¹ ; ^* ; Jorge M. Santos¹ ; ^* ; Mariana Teixeira¹ ; Mariana Filipe¹ ; Ana Rita S. Pereira² ; Augusto Ministro² ; ³ ; Ana Á ; gua-Doce⁴ ; Manuela Carvalheiro⁵ ; Maria Manuela Gaspar⁵ ; Joana P. Miranda⁵ ; Luis Graç ; a⁴ ; Sandra Simõ ; es⁵ ; Susana Constantino Rosa Santos² ; ⁶ ; Pedro Cruz¹ ; Helder Cruz¹ ; ^{helder.cruz@ecbio.com}
• 关键词：advanced-therapy medicinal product ; cryopreservation ; mesenchymal stromal cells ; potency ; thawing
• 刊名：Cytotherapy
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：19
• 期：3
• 页码：360-370
• 全文大小：1533 K
• 卷排序：19

文摘

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®.MethodsCell 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.ResultsPhenotype 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.DiscussionThis 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.