Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells

Fernández-Rebollo, Eduardo; Mentrup, Birgit; Ebert, Regina; Franzen, Julia; Abagnale, Giulio; Sieben, Torsten; Ostrowska, Alina; Hoffmann, Per; Roux, Pierre-François; Rath, Björn; Goodhardt, Michèle; Lemaı̂tre, Jean-Marc; Bischof, Oliver; Jakob, Franz; Wagner, Wolfgang

doi:10.1038/s41598-017-05207-1

Cited by 66 publications

(65 citation statements)

References 29 publications

(42 reference statements)

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“…Unlike in other studies, here ASCs were expanded using human platelet lysate in the culture media, which may have the advantage of avoiding the use of animal‐derived factors. Human platelet lysate is widely used to grow MSCs, and many studies have demonstrated that this confers a degree of safety that is at least equivalent to that offered by fetal bovine serum . Indeed, some studies have suggested that the use of platelet lysate may increase cell yield and shorten the time for ex vivo expansion without epigenetic alterations …”

Section: Discussionmentioning

confidence: 99%

“…Human platelet lysate is widely used to grow MSCs, [23][24][25] and many studies have demonstrated that this confers a degree of safety that is at least equivalent to that offered by fetal bovine serum. 26,27 Indeed, some studies have suggested that the use of platelet lysate may increase cell yield and shorten the time for ex vivo expansion without epigenetic alterations. 25,27 One of the issues regarding the use of somatic cell medicinal products has been the selection of the cell dose.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 Indeed, some studies have suggested that the use of platelet lysate may increase cell yield and shorten the time for ex vivo expansion without epigenetic alterations. 25,27 One of the issues regarding the use of somatic cell medicinal products has been the selection of the cell dose. In general, decisions regarding dose levels were based on studies performed in animals, the absence of AEs, and the number of cells that can be generated in a particular period.…”

Section: Discussionmentioning

confidence: 99%

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Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

García‐Arranz

García-Olmo

Herreros

et al. 2019

Stem Cells Translational Medicine

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“…Mesenchymal stem cells were isolated from the bone marrow of donors undergoing orthopedic surgery (n = 11; BM-MSC RWTH Aachen) (Fernandez-Rebollo et al 2017), from bone marrow aspirates of allogeneic hematopoietic stem cell donors (n = 8; BM-MSC University of Heidelberg) (Horn et al 2008), from subcutaneous adipose tissue lipoaspirates (n = 3, AT-MSC RWTH Aachen) (Cholewa et al 2011) and from umbilical cord pieces (n = 2; UCP-MSC; University of Hannover) (Selich et al 2016). Fibroblasts were isolated from dermis (n = 4; RWTH Aachen) (Koch et al 2012).…”

Section: Cell Culturementioning

confidence: 99%

Epigenetic drift during long-term culture of cells in vitro

Franzen

Georgomanolis

Selich

et al. 2018

Preprint

Self Cite

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Replicative senescence of cells in culture is associated with highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. Thus far, it is largely unclear if these epigenetic modifications are directly regulated, or if they are randomly evoked by other chromatin changes during long-term culture.We have identified CG dinucleotides (CpGs) that become continuously hyper-or hypomethylated in the course of culture expansion of mesenchymal stem cells (MSCs) and other cell types. These modifications provide a biomarker for replicative senescence and correlate with the number of passages in vitro. During reprogramming into induced pluripotent stem cells (iPSCs) senescence-associated DNAm is reversed simultaneously with pluripotency-associated DNAm changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that upon passaging the DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development. Notably, BBA-seq of hairpin-linked DNA molecules demonstrated that many CpG dyads are methylated only on the forward or the reverse strand. This hemimethylation was conserved over many passages, indicating that it was not due to insufficient maintenance of DNAm patterns. Circularized chromatin conformation capture (4C) of senescence-associated CpGs revealed reproducible changes during senescence without evidence for preferential interaction between CpGs that become either hyper-or hypomethylated.Taken together, senescence-associated DNAm fluctuates stochastically at specific sites in the genome. Strand-specific DNAm and reproducible changes in 4C indicate that epigenetic modifications of these CG dyads are not regulated in a targeted manner but rather caused by passage-specific higher order chromatin conformation states.

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“…Moreover, human PL preconditioned CD34+/CD133+-enriched bone marrow-derived progenitor cells were successfully used to improve vascularization in tissue-engineered constructs in vivo [25]. FernandezRebollo et al [26] strived to investigate the safety of human PL as a culture supplement and were able to show robust expansion of bone marrow-derived MSCs without significant changes in the DNA-methylation profiles, cytoskeletal organization, or focal adhesion. The supplementation with PL has been applied in a plethora of in vitro cell culture protocols.…”

Section: Prp and Pl As An Autologous Cell Culture Supplementmentioning

confidence: 99%

Platelet-Rich Plasma in Tissue Engineering: Hype and Hope

Lang

Loibl²,

Herrmann³

2018

Eur Surg Res

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Background: Platelet-rich plasma (PRP) refers to an enriched platelet suspension in plasma. In addition to the clinical application of PRP in the context of various orthopedic diseases and beyond, PRP and platelet lysate (PL) have been in focus in the field of tissue engineering. In this review, we discuss the application of PRP as a cell culture supplement and as part of tissue engineering strategies, particularly emphasizing current hurdles and ambiguities regarding the efficacy of PRP in these approaches. Summary: As a putative autologous replacement for animal-derived supplements such as fetal calf serum (FCS), PRP has been applied as cell culture supplement for the expansion of stem and progenitor cells for tissue engineering applications and cell therapies. Attributed to the high content of growth factors in platelets, PRP has been shown to promote cell growth, which was mostly superior to standard cultures supplemented with FCS, while the differentiation capacity of progenitor cells seems not to be affected. However, it was also suggested that cultivation of cells with PRP significantly alters the protein expression profile in cells in comparison to FCS, indicating that the influence of PRP on cell behavior should be thoroughly investigated. Moreover, different PRP preparation methods and donor variations have to be considered for the use of PRP under good manufacturing practice conditions. PRP has been used for various tissue engineering applications in the context of bone, cartilage, skin, and soft tissue repair, where most studies were conducted in the field of bone tissue engineering. These approaches take either advantage of the release of chemoattractive, angiogenic, proliferative, and putatively pro-regenerative growth factors from PRP, and/or the hydrogel properties of activated PRP, making it suitable as a cell delivery vehicle. In many of these studies, PRP is combined with biomaterials, cells, and in some cases recombinant growth factors. Although the experimental design often does not allow conclusions on the pro-regenerative effect of PRP itself, most publications report beneficial effects if PRP is added to the tissue-engineered construct. Furthermore, it was demonstrated that the release of growth factors from PRP may be tailored and controlled when PRP is combined with materials able to capture growth factors. Key Messages: Platelet-derived preparations such as PRP and PL represent a promising source of autologous growth factors, which may be applied as cell culture supplement or to promote regeneration in tissue-engineered constructs. Furthermore, activated PRP is a promising candidate as an autologous cell carrier. However, the studies investigating PRP in these contexts often show conflicting results, which most likely can be attributed to the lack of standardized preparation methods, particularly with regard to the platelet content and donor variation of PRP. Ultimately, the use of PRP has to be tailored for the individual application.

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Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells

Cited by 66 publications

References 29 publications

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Autologous adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistula: A randomized clinical trial with long-term follow-up

Epigenetic drift during long-term culture of cells in vitro

Platelet-Rich Plasma in Tissue Engineering: Hype and Hope

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