A Blood Bank Standardized Production of Human Platelet Lysate for Mesenchymal Stromal Cell Expansion: Proteomic Characterization and Biological Effects

Andrea Bianchetti, Clizia Chinello, Michele Guindani, Simona Braga, Arabella Neva, Rosanna Verardi, Giovanna Piovani, Lisa Pagani, Gina Lisignoli, Fulvio Magni, Domenico Russo, Camillo Almici

Research output: Contribution to journalArticlepeer-review

Abstract

Human platelet lysate (hPL) is considered a valid substitute to fetal bovine serum (FBS) in the expansion of mesenchymal stromal cells (MSC), and it is commonly produced starting from intermediate side products of whole blood donations. Through freeze-thaw cycles, hPL is highly enriched in chemokines, growth factors, and adhesion and immunologic molecules. Cell therapy protocols, using hPL instead of FBS for the expansion of cells, are approved by regulatory authorities without concerns, and its administration in patients is considered safe. However, published data are fairly difficult to compare, since the production of hPL is highly variable. This study proposes to optimize and standardize the hPL productive process by using instruments, technologies, and quality/safety standards required for blood bank activities and products. The quality and improved selection of the starting material (i.e., the whole blood), together with the improvement of the production process, guarantee a product characterized by higher content and quality of growth factors as well as a reduction in batch-to-batch variability. By increasing the number of freeze/thaw cycles from one (hPL1c) to four (hPL4c), we obtained a favorable effect on the release of growth factors from platelet α granules. Those changes have directly translated into biological effects leading to a decreasing doubling time (DT) of MSC expansion at 7 days (49.41 ± 2.62 vs. 40.61 ± 1.11 h, p < 0.001). Furthermore, mass spectrometry (MS)-based evaluation has shown that the proliferative effects of hPL4c are also combined with a lower batch-to-batch variability (10-15 vs. 21-31%) at the proteomic level. In conclusion, we have considered lot-to-lot hPL variability, and by the strict application of blood bank standards, we have obtained a standardized, reproducible, safe, cheap, and ready-to-use product.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - May 14 2021

Keywords

  • blood banks standards
  • growth factors
  • human platelet lysate
  • mass spectrometry
  • mesenchymal stromal cells

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