Background and Objectives The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl sub(2)-activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. Materials and Methods PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl sub(2)-activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). Results PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. Conclusions The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs.