Platelet lysate induces chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells

Hassan, Ghmkin; Bahjat, Mohammad; Kasem, Issam; Soukkarieh, Chadi; Aljamali, Majd

doi:10.1186/s11658-018-0080-6

Cited by 18 publications

(15 citation statements)

References 23 publications

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“…This might be due to the synergistic effect of PL and CS on chondrogenic differentiation. As observed in previous studies, PL induces chondrogenic differentiation of adipose-derived [89] and umbilical cord-derived [52] MSCs. It has been shown that PL-loaded hyaluronic acid stimulates chondrogenesis of hMSCs [90].…”

Section: Discussionsupporting

confidence: 85%

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel

et al. 2020

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Background Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy. Methods In this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v) and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC)-loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA. Results Viability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation. Conclusions It is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis. Graphical abstract

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Section: Discussionsupporting

confidence: 85%

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel

et al. 2020

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show abstract

“…This might be due to the synergistic effect of PL and CS on chondrogenic differentiation. As observed in previous studies, PL induces chondrogenic differentiation of adipose-derived [89] and umbilical cord-derived [52] MSCs. It has been shown that PLloaded hyaluronic acid stimulates chondrogenesis of h MSCs [90].…”

Section: Discussionsupporting

confidence: 85%

Inhibition of Hypertrophy and Improving Chondrocyte Differentiation by MMP-13 Inhibitor Small Molecule-Encapsulated in Alginate-Chondroitin Sulfate-Platelet Lysate Hydrogel

Jahangir

Eglin²,

Pötter

et al. 2020

Preprint

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Background Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix Metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy.Methods In this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v), and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC) loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA.Results Viability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation.Conclusions It is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis.

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“…Schallmoser et al and Capelli et al also reported the feasibility of clinical scale expansion of MSCs from BM aspirate without any prior manipulation using HPL . It has also been reported that use of HPL enhances osteogenic and chondrogenic differentiation capabilities of MSCs in vitro .…”

Section: Introductionmentioning

confidence: 95%

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

Gupta

Hall

Geris

et al. 2019

Stem Cells Translational Medicine

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Xenogeneic‐free media are required for translating advanced therapeutic medicinal products to the clinics. In addition, process efficiency is crucial for ensuring cost efficiency, especially when considering large‐scale production of mesenchymal stem cells (MSCs). Human platelet lysate (HPL) has been increasingly adopted as an alternative for fetal bovine serum (FBS) for MSCs. However, its therapeutic and regenerative potential in vivo is largely unexplored. Herein, we compare the effects of FBS and HPL supplementation for a scalable, microcarrier‐based dynamic expansion of human periosteum‐derived cells (hPDCs) while assessing their bone forming capacity by subcutaneous implantation in small animal model. We observed that HPL resulted in faster cell proliferation with a total fold increase of 5.2 ± 0.61 in comparison to 2.7 ± 02.22‐fold in FBS. Cell viability and trilineage differentiation capability were maintained by HPL, although a suppression of adipogenic differentiation potential was observed. Differences in mRNA expression profiles were also observed between the two on several markers. When implanted, we observed a significant difference between the bone forming capacity of cells expanded in FBS and HPL, with HPL supplementation resulting in almost three times more mineralized tissue within calcium phosphate scaffolds. FBS‐expanded cells resulted in a fibrous tissue structure, whereas HPL resulted in mineralized tissue formation, which can be classified as newly formed bone, verified by μCT and histological analysis. We also observed the presence of blood vessels in our explants. In conclusion, we suggest that replacing FBS with HPL in bioreactor‐based expansion of hPDCs is an optimal solution that increases expansion efficiency along with promoting bone forming capacity of these cells. Stem Cells Translational Medicine 2019;8:810&821

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Platelet lysate induces chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells

Cited by 18 publications

References 23 publications

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel

Inhibition of Hypertrophy and Improving Chondrocyte Differentiation by MMP-13 Inhibitor Small Molecule-Encapsulated in Alginate-Chondroitin Sulfate-Platelet Lysate Hydrogel

Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture

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