Human Platelet Lysate for Good Manufacturing Practice-Compliant Cell Production

Abstract

Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free cell propagation with highly efficient stimulation of cell proliferation, enabling humanized manufacturing of cell therapeutics within a reasonable timeframe. Providers of HPL have to consider dedicated quality issues regarding identity, purity, potency, traceability and safety. Release criteria have to be defined, characterizing the suitability of HPL batches for the support of a specific cell culture. Fresh or expired platelet concentrates from healthy blood donors are the starting material for HPL preparation, according to regulatory requirements. Pooling of individual platelet lysate units into one HPL batch can balance donor variation with regard to essential platelet-derived growth factors and cytokines. The increasingly applied pathogen reduction technologies will further increase HPL safety. In this review article, aspects and regulatory requirements of whole blood donation and details of human platelet lysate manufacturing are presented. International guidelines for raw materials are discussed, and defined quality controls, as well as release criteria for safe and GMP-compliant HPL production, are summarized.

Synergy of Human Platelet-Derived Extracellular Vesicles with Secretome Proteins Promotes Regenerative Functions

“…Pooled HPL was prepared as described [ 12 ]. In brief, after written informed consent about the use of residual material, 10 expired buffy-coat derived platelet concentrates from a total of 40 healthy blood donors were frozen at −30 °C overnight.…”

“…Several groups are therefore evaluating the applicability of novel platelet derivatives, including human platelet lysate (HPL), for regenerative purposes [ 9 , 10 ]. HPL attracted particular attention as a promising raw material for cell therapy manufacture and it can be prepared cost-effectively via lysis of outdated clinical platelet concentrates [ 11 , 12 ]. We have recently demonstrated that HPL can also significantly accelerate human skin-organoid formation in vitro and wound healing in vivo [ 13 ].…”

Processing and Ex Vivo Expansion of Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells for the Development of an Advanced Therapy Medicinal Product for use in Humans

“…Moreover, PL does not affect the BM-MSC immunophenotype, trilineage differentiation potential, immunomodulatory properties, relate telomere length, or chromosomal stability when compared to FBS-supplemented cultures [39,40]. During the selection of manufacturer of PL, it is necessary to verify the quality specification of the PL according to the aspects presented by Oeller et al [41]. Although on the market there are a few chemically defined media [42] and some of them were tested during our optimization research, we did not select one of them for use in our manufacturing process to simplify work (minimize the amount of manipulation it was necessary to conduct) in the cleanroom and to slightly reduce the manufacturing costs.…”

Improving Human Induced Pluripotent Stem Cell-Derived Megakaryocyte Differentiation and Platelet Production

“…Another interest behind our efforts was the in vitro propagation of hiPSC-derived platelets as an ideally well-defined sustainable source of pro-angiogenic and regenerative factors for good manufacturing practice (GMP)-compliant cell production and regeneration [ 46 , 47 ]. Human platelet lysate (HPL) derived from donor platelets has replaced fetal bovine serum as a key cell culture supplement particularly for clinical-grade advanced therapy medicinal product (ATMP) manufacture [ 26 , 48 ].…”