Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell &amp; Gene Therapy

Fernández‐Muñoz, Beatriz; Pati, Shibani; Schäfer, Richard

doi:10.1016/j.jcyt.2019.06.006

Cited by 48 publications

(61 citation statements)

References 107 publications

(115 reference statements)

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“…At this time, according to our findings, not enough information is available due to a lack of universally accepted international guidelines for hPL preparation and analysis. Recently, in response to similar results reported elsewhere, a collaboration between the American Association of Blood Banks (AABB) and the International Society of Cell Therapy was initiated to address hPL quality control and standardize hPL manufacturing [30,73].…”

Section: Discussionmentioning

confidence: 94%

Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review

et al. 2020

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Background Foetal bovine serum (FBS), is the most commonly used culture medium additive for in vitro cultures, despite its undefined composition, its potential immunogenicity and possible prion/zoonotic transmission. For these reasons, significant efforts have been targeted at finding a substitute, such as serum free-media or human platelet-lysates (hPL). Our aim is to critically appraise the state-of-art for hPL in the published literature, comparing its impact with FBS. Materials and methods In June 2019 a systematic search of the entire Web of Science, Medline and PubMed database was performed with the following search terms: (mesenchymal stem cells) AND (fetal bovine serum OR fetal bovine calf) AND (human platelet lysate). Excluded from this search were review articles that were published before 2005, manuscripts in which mesenchymal stem cells (MSCs) were not from human sources, and when the FBS controls were missing. Results Based on our search algorithm, 56 papers were selected. A review of these papers indicated that hMSCs cultured with hPL showed a spindle-shaped elongated morphology, had higher proliferation indexes, similar cluster of differentiation (CD) markers and no significant variation in differentiation lineage (osteocyte, adipocyte, and chondrocyte) compared to those cultured with FBS. Main sources of primary hMSCs were either fat tissue or bone marrow; in a few studies cells isolated from alternative sources showed no relevant difference in their response. Conclusion Despite the difference in medium choice and a lack of standardization of hPL manufacturing, the majority of publications support that hPL was at least as effective as FBS in promoting adhesion, survival and proliferation of hMSCs. We conclude that hPL should be considered a viable alternative to FBS in hMSCs culture—especially with a view for their clinical use.

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Section: Discussionmentioning

confidence: 94%

Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review

et al. 2020

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“…The risk of infection from animal-derived products is especially pertinent during this unique time in the history of the viral pandemic disease [34]. Clinical trials evaluating the potential of stem cell therapies are growing faster than research that investigates alternative, xenogeneic-free methods for cell isolation and culture [35][36][37]. Considering the therapeutic potential of hADSC, in particular for peripheral nerve repair, we established a complete xenofree protocol for cell culture isolation and expansion.…”

Section: Discussionmentioning

confidence: 99%

Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells

et al. 2020

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Background The autologous nerve graft, despite its donor site morbidity and unpredictable functional recovery, continues to be the gold standard in peripheral nerve repair. Rodent research studies have shown promising results with cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit, as an alternative strategy for nerve regeneration. To achieve meaningful clinical translation, cell therapy must comply with biosafety. Cell extraction and expansion methods that use animal-derived products, including enzymatic adipose tissue dissociation and the use of fetal bovine serum (FBS) as a culture medium supplement, have the potential for transmission of zoonotic infectious and immunogenicity. Human-platelet-lysate (hPL) serum has been used in recent years in human cell expansion, showing reliability in clinical applications. Methods We investigated whether hADSC can be routinely isolated and cultured in a completely xenogeneic-free way (using hPL culture medium supplement and avoiding collagenase digestion) without altering their physiology and stem properties. Outcomes in terms of stem marker expression (CD105, CD90, CD73) and the osteocyte/adipocyte differentiation capacity were compared with classical collagenase digestion and FBS-supplemented hADSC expansion. Results We found no significant differences between the two examined extraction and culture protocols in terms of cluster differentiation (CD) marker expression and stem cell plasticity, while hADSC in hPL showed a significantly higher proliferation rate when compared with the usual FBS-added medium. Considering the important key growth factors (particularly brain-derived growth factor (BDNF)) present in hPL, we investigated a possible neurogenic commitment of hADSC when cultured with hPL. Interestingly, hADSC cultured in hPL showed a statistically higher secretion of neurotrophic factors BDNF, glial cell-derived growth factor (GDNF), and nerve-derived growth factor (NFG) than FBS-cultured cells. When cocultured in the presence of primary neurons, hADSC which had been grown under hPL supplementation, showed significantly enhanced neurotrophic properties. Conclusions The hPL-supplement medium could improve cell proliferation and neurotropism while maintaining stable cell properties, showing effectiveness in clinical translation and significant potential in peripheral nerve research.

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“…International blood authorities advise a minimum interval of 3 months between blood donations to allow for repeated viral testing to minimize the risk of disease transmission via platelet products. In the context of HPL, this is especially relevant when smaller PC-pool sizes are used (≤ 16 donors) and where pathogen reduction is not applied [ 6 ]. In the present study, HPL produced from PCs stored for > 4 months showed a significant deterioration of several cytokines relevant for MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Supplements providing growth factors (GFs), proteins, and enzymes for ex vivo MSC expansion are broadly categorized as xenogeneic (animal-derived), xeno-free (human-derived), or chemically defined [ 3 , 4 ]. Although fetal bovine serum (FBS) is commonly used for MSC expansion [ 5 ], several limitations of FBS supplementation have been highlighted [ 3 , 6 ]. European guidelines advocate the use of “non-ruminant” over “ruminant materials” for the manufacture of human medicinal products [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Pooled- and/or single-donor apheresis PCs are routinely prepared by blood establishments for transfusion and, depending on local regulations, stored for a maximum of 4–7 days before being discarded [ 9 ]. It is estimated that 5–20% of PCs produced in transfusion centers become “outdated” and utilizing these for HPL production is reported to be an ethically and economically optimal strategy, due to comparable efficacy of HPL produced from “fresh” and outdated PCs [ 6 ]. The current literature consistently demonstrates that HPL is at least comparable, and often superior, to FBS in supporting MSC proliferation, stromal phenotype, chromosomal stability, and multi-lineage differentiation potential [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Influence of platelet storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering

et al. 2020

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Background Human platelet lysate (HPL) is emerging as the preferred xeno-free supplement for the expansion of mesenchymal stromal cells (MSCs) for bone tissue engineering (BTE) applications. Due to a growing demand, the need for standardization and scaling-up of HPL has been highlighted. However, the optimal storage time of the source material, i.e., outdated platelet concentrates (PCs), remains to be determined. The present study aimed to determine the optimal storage time of PCs in terms of the cytokine content and biological efficacy of HPL. Methods Donor-matched bone marrow (BMSCs) and adipose-derived MSCs (ASCs) expanded in HPL or fetal bovine serum (FBS) were characterized based on in vitro proliferation, immunophenotype, and multi-lineage differentiation. Osteogenic differentiation was assessed at early (gene expression), intermediate [alkaline phosphatase (ALP) activity], and terminal stages (mineralization). Using a multiplex immunoassay, the cytokine contents of HPLs produced from PCs stored for 1–9 months were screened and a preliminary threshold of 4 months was identified. Next, HPLs were produced from PCs stored for controlled durations of 0, 1, 2, 3, and 4 months, and their efficacy was compared in terms of cytokine content and BMSCs’ proliferation and osteogenic differentiation. Results BMSCs and ASCs in both HPL and FBS demonstrated a characteristic immunophenotype and multi-lineage differentiation; osteogenic differentiation of BMSCs and ASCs was significantly enhanced in HPL vs. FBS. Multiplex network analysis of HPL revealed several interacting growth factors, chemokines, and inflammatory cytokines. Notably, stem cell growth factor (SCGF) was detected in high concentrations. A majority of cytokines were elevated in HPLs produced from PCs stored for ≤ 4 months vs. > 4 months. However, no further differences in PC storage times between 0 and 4 months were identified in terms of HPLs’ cytokine content or their effects on the proliferation, ALP activity, and mineralization of BMSCs from multiple donors. Conclusions MSCs expanded in HPL demonstrate enhanced osteogenic differentiation, albeit with considerable donor variation. HPLs produced from outdated PCs stored for up to 4 months efficiently supported the proliferation and osteogenic differentiation of MSCs. These findings may facilitate the standardization and scaling-up of HPL from outdated PCs for BTE applications.

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Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy

Cited by 48 publications

References 107 publications

Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review

Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review

Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells

Influence of platelet storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering

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