Human Platelet Lysate Stimulated Adipose Stem Cells Exhibit Strong Neurotrophic Potency for Nerve Tissue Engineering Applications

Lischer, Mirko; Summa, Pietro G. di; Oranges, Carlo M.; Schaefer, Dirk J.; Kalbermatten, Daniel F.; Guzman, Raphaël; Madduri, Srinivas

doi:10.2217/rme-2020-0031

Cited by 15 publications

(12 citation statements)

References 41 publications

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“…This effect seemed mainly cell-interaction related, as non-conditioned medium, despite containing a relevant amount of growth factors, did not influence significantly neurite outgrowth. Similar outcomes of the enhanced neurotrophic potential of hADSC in response to HPL-conditioning were reported recently in a co-culture in vitro model with chicken embryonic DRG [51]. Whether such factors could be internalized by cells during culture [52] and potentially released or influencing hADSC gene/protein expression will be a matter of further in vitro studies of our group, together with in vivo applications.…”

Section: Discussionsupporting

confidence: 78%

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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Section: Discussionsupporting

confidence: 78%

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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“…As a medium additive, hPL provides a safe, human-derived product, which has been shown to increase the proliferation of hADSC, preserve their stemness properties and differentiation potential, and even enhance their neural commitment (Guiotto et al, 2020;Lischer et al, 2020;Palombella et al, 2020). For all these reasons, hADSC pre-expanded in hPL (hADSC hPL ) are the ideal candidate for cell-based therapies and can play a role in nerve tissue engineering encouraging regeneration.…”

Section: Discussionmentioning

confidence: 99%

Human Platelet Lysate Acts Synergistically With Laminin to Improve the Neurotrophic Effect of Human Adipose-Derived Stem Cells on Primary Neurons in vitro

Guiotto

Raffoul

Hart

et al. 2021

Front. Bioeng. Biotechnol.

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BackgroundDespite the advancements in microsurgical techniques and noteworthy research in the last decade, peripheral nerve lesions have still weak functional outcomes in current clinical practice. However, cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit has shown promising results in animal studies. Human platelet lysate (hPL) has been adopted to avoid fetal bovine serum (FBS) in consideration of the biosafety concerns inherent with the use of animal-derived products in tissue processing and cell culture steps for translational purposes. In this work, we investigate how the interplay between hPL-expanded hADSC (hADSChPL) and extracellular matrix (ECM) proteins influences key elements of nerve regeneration.MethodshADSC were seeded on different ECM coatings (laminin, LN; fibronectin, FN) in hPL (or FBS)-supplemented medium and co-cultured with primary dorsal root ganglion (DRG) to establish the intrinsic effects of cell–ECM contact on neural outgrowth. Co-cultures were performed “direct,” where neural cells were seeded in contact with hADSC expanded on ECM-coated substrates (contact effect), or “indirect,” where DRG was treated with their conditioned medium (secretome effect). Brain-derived nerve factor (BDNF) levels were quantified. Tissue culture plastic (TCPS) was used as the control substrate in all the experiments.ResultshPL as supplement alone did not promote higher neurite elongation than FBS when combined with DRG on ECM substrates. However, in the presence of hADSC, hPL could dramatically enhance the stem cell effect with increased DRG neurite outgrowth when compared with FBS conditions, regardless of the ECM coating (in both indirect and direct co-cultures). The role of ECM substrates in influencing neurite outgrowth was less evident in the FBS conditions, while it was significantly amplified in the presence of hPL, showing better neural elongation in LN conditions when compared with FN and TCPS. Concerning hADSC growth factor secretion, ELISA showed significantly higher concentrations of BDNF when cells were expanded in hPL compared with FBS-added medium, without significant differences between cells cultured on the different ECM substrates.ConclusionThe data suggest how hADSC grown on LN and supplemented with hPL could be active and prone to support neuron–matrix interactions. hPL enhanced hADSC effects by increasing both proliferation and neurotrophic properties, including BDNF release.

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“…In addition, no sign of teratogenicity has been observed. Recent studies also suggested the benefits of HPLs for expanding differentiated human cells and immune cells [ 39 ], and enhancing the neurotrophic potency of adipose tissue-derived MSCs through promotion of axonal outgrowth, suggesting applications in nerve tissue engineering [ 40 ] and human cell therapies [ 41 ]. Therefore, multiple studies have unambiguously demonstrated the non-toxicity and functional activities of HPLs preparations across a large range of cell types [ 39 ].…”

Section: Platelet Lysates In Regenerative Medicine and Cell Therapy: ...mentioning

confidence: 99%

Can the administration of platelet lysates to the brain help treat neurological disorders?

Nebie

Buée

Blum

et al. 2022

Cell. Mol. Life Sci.

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Neurodegenerative disorders of the central nervous system (CNS) and brain traumatic insults are characterized by complex overlapping pathophysiological alterations encompassing neuroinflammation, alterations of synaptic functions, oxidative stress, and progressive neurodegeneration that eventually lead to irreversible motor and cognitive dysfunctions. A single pharmacological approach is unlikely to provide a complementary set of molecular therapeutic actions suitable to resolve these complex pathologies. Recent preclinical data are providing evidence-based scientific rationales to support biotherapies based on administering neurotrophic factors and extracellular vesicles present in the lysates of human platelets collected from healthy donors to the brain. Here, we present the most recent findings on the composition of the platelet proteome that can activate complementary signaling pathways in vivo to trigger neuroprotection, synapse protection, anti-inflammation, antioxidation, and neurorestoration. We also report experimental data where the administration of human platelet lysates (HPL) was safe and resulted in beneficial neuroprotective effects in established rodent models of neurodegenerative diseases such as Parkinson’s disease, Alzheimer's disease, traumatic brain injury, and stroke. Platelet-based biotherapies, prepared from collected platelet concentrates (PC), are emerging as a novel pragmatic and accessible translational therapeutic strategy for treating neurological diseases. Based on this assumption, we further elaborated on various clinical, manufacturing, and regulatory issues that need to be addressed to ensure the ethical supply, quality, and safety of HPL preparations for treating neurodegenerative and traumatic pathologies of the CNS. HPL made from PC may become a unique approach for scientifically based treatments of neurological disorders readily accessible in low-, middle-, and high-income countries. Graphical abstract

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Human Platelet Lysate Stimulated Adipose Stem Cells Exhibit Strong Neurotrophic Potency for Nerve Tissue Engineering Applications

Cited by 15 publications

References 41 publications

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

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

Human Platelet Lysate Acts Synergistically With Laminin to Improve the Neurotrophic Effect of Human Adipose-Derived Stem Cells on Primary Neurons in vitro

Can the administration of platelet lysates to the brain help treat neurological disorders?

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