Scale-Up of Academic Mesenchymal Stromal Cell Production

扩大学术间充质基质细胞的生产

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作者:Caroline Laroye, Mélanie Gauthier, Jessica Morello, Naceur Charif, Véronique Latger Cannard, Céline Bonnet, Alain Lozniewski, Andrei Tchirkov, Natalia De Isla, Véronique Decot, Loïc Reppel, Danièle Bensoussan

Background

Many clinical trials have reported the use of mesenchymal stromal cells (MSCs) following the indication of severe SARS-CoV-2 infection. However, in the COVID19 pandemic context, academic laboratories had to adapt a production process to obtain MSCs in a very short time. Production processes, especially freezing/thawing cycles, or culture medium have impacts on MSC properties. We evaluated the impact of an intermediate cryopreservation state during MSC culture to increase production yields.

Conclusions

Intermediate cryopreservation allows an increase in the production yield and has little impact on the basic characteristics of MSCs.

Methods

Seven Wharton's jelly (WJ)-MSC batches generated from seven different umbilical cords with only one cryopreservation step and 13 WJ-MSC batches produced with intermediate freezing were formed according to good manufacturing practices. The identity (phenotype and clonogenic capacities), safety (karyotype, telomerase activity, sterility, and donor qualification), and functionality (viability, mixed lymphocyte reaction) were analyzed.

Results

No significant differences between MSC production processes were observed, except for the clonogenic capacity, which was decreased, although it always remained above our specifications. Conclusions: Intermediate cryopreservation allows an increase in the production yield and has little impact on the basic characteristics of MSCs.

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