Survey on manufacturing MSCs for the treatment of graft-versus-host disease

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that showed promising activity for the treatment of steroid-resistant acute graft-versus-host disease (SR aGvHD). Cristina Trento from King’s College London, London, UK, Maria Ester Bernardo from San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, Milan, Italy, and colleagues analyzed MSC manufacturing with a two-phase questionnaire across 17 European Society for Blood and Marrow Transplantation (EBMT) centers. Data was published in Biology of Blood and Marrow Transplantation.

More than 1500 MSC treatments have been performed in the 17 EBMT centers that were included in this study.

Key findings:

• MSCs were produced from bone marrow in 88% of cases, two centers manufactured MSCs from umbilical cord blood or cord tissue
• Manufacturing process: fetal bovine serum was replaced with human platelet lysate in several cases
  • hPL (blood bank): 54%
  • hPL (commercially available): 23%
  • FBS: 23%
• 59% of centers used exclusively third-party MSCs, whilst one facility produced only autologous MSCs
• 71% of the centers used MSCs from frozen batches, 29% used fresh/frozen products
• Significant heterogeneity in product specification was found, most of the centers used CD19, CD34, CD14, HLA-DR and CD3 negativity, whereas fewer centers analyzed the expression of CD166, CD31 and CD44

In summary, this data indicates that there are inconsistent methods in MSC manufacturing and release criteria. The study group stated that there is a need for a mechanistic potency assay. “Until more informative potency assays become available, a more homogeneous approach to cell production may at least reduce variability in clinical trials and improve interpretation of results.”