Human platelet lysate can replace fetal bovine serum for clinical‐scale expansion of functional mesenchymal stromal cells

TLDR

Human mesenchymal stromal cells hold promise for regenerative and immunomodulatory therapies, but their clinical translation has been hindered by reliance on fetal bovine serum. The study evaluated human platelet lysate as a substitute for fetal bovine serum in a two‑step, clinical‑scale MSC expansion protocol. Human platelet lysate, produced from buffy coats and characterized by a distinct growth‑factor profile, proved more efficient than fetal bovine serum, yielding up to 5.4 × 10⁸ MSCs per 3 × 10⁵ seed cells, while maintaining immunophenotype, differentiation capacity, and non‑tumorigenicity, and eliminating bovine prion, viral, and zoonotic contamination.

Abstract

BACKGROUND: Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS). STUDY DESIGN AND METHODS: The capacity of human platelet lysate (HPL) to replace FBS for clinical-scale MSC propagation was analyzed. RESULTS: HPL could be efficiently produced from buffy coats. Multiplex analyses allowed a distinct HPL growth factor profile to be delineated. With a previously established two-step clinical-scale procedure, HPL was reproducibly more efficient than FBS in supporting MSC outgrowth. With only 3 × 105 primary culture-derived MSCs, a mean of 4.36 × 108 HPL-MSCs (range, 3.01 × 108-5.40 × 108) was obtained within a single secondary 11- to 13-day culture step. Although morphologically distinct, HPL-MSCs and FBS-MSCs did not differ significantly in terms of immunophenotype, differentiation potential in vitro, and lack of tumorigenicity in nude mice in vivo. CONCLUSIONS: Replacing FBS with HPL prevents bovine prion, viral, and zoonose contamination of the stem cell product. This new efficient FBS-free two-step procedure for clinical-scale MSC propagation may represent a major step toward challenging new stem cell therapies.