The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche

Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, pla...

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Main Authors: Melinda Simon, Bálint Major, Gabriella Vácz, Olga Kuten, István Hornyák, Adél Hinsenkamp, Dorottya Kardos, Marcell Bagó, Domonkos Cseh, Adrienn Sárközi, Denes Horvathy, Stefan Nehrer, Zsombor Lacza
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/4854619
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author Melinda Simon
Bálint Major
Gabriella Vácz
Olga Kuten
István Hornyák
Adél Hinsenkamp
Dorottya Kardos
Marcell Bagó
Domonkos Cseh
Adrienn Sárközi
Denes Horvathy
Stefan Nehrer
Zsombor Lacza
author_facet Melinda Simon
Bálint Major
Gabriella Vácz
Olga Kuten
István Hornyák
Adél Hinsenkamp
Dorottya Kardos
Marcell Bagó
Domonkos Cseh
Adrienn Sárközi
Denes Horvathy
Stefan Nehrer
Zsombor Lacza
author_sort Melinda Simon
collection DOAJ
description Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as “proliferative agents” for the topical MSC pool. Hyperacute serum (HAS), a new serum derivative, has been designed to approximate the natural coagulation cascade with a single-step, additive-free preparation method. We investigated the effects of HAS on monolayer MSC cultures and in their natural niche, in 3D subchondral bone and marrow explants. Viability measurements, RT-qPCR evaluation for gene expression and flow cytometry for cell surface marker analysis were performed to compare the effects of FCS-, PRP-, or HAS-supplemented culture media. Monolayer MSCs showed significantly higher metabolic activity following 5 days’ incubation in HAS, and osteoblast-specific mRNA expression was markedly increased, while cells also retained their MSC-specific cell surface markers. A similar effect was observed on bone and marrow explants, which was further confirmed with confocal microscopy analysis. Moreover, markedly higher bone marrow preservation was observed with histology in case of HAS supplementation compared to FCS. These findings indicate possible application of HAS in regenerative solutions of skeletal diseases like OA or osteonecrosis.
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spelling doaj-art-ccfe9913152c4f7a8f5add8eaae197f62025-02-03T01:09:42ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/48546194854619The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow NicheMelinda Simon0Bálint Major1Gabriella Vácz2Olga Kuten3István Hornyák4Adél Hinsenkamp5Dorottya Kardos6Marcell Bagó7Domonkos Cseh8Adrienn Sárközi9Denes Horvathy10Stefan Nehrer11Zsombor Lacza12Institute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryDepartment of Orthopedics, Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryOrthosera GmbH, Krems an der Donau, AustriaInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University, Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryDanube University Krems, Krems an der Donau, AustriaInstitute of Clinical Experimental Research, Semmelweis University, Budapest, HungaryMesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as “proliferative agents” for the topical MSC pool. Hyperacute serum (HAS), a new serum derivative, has been designed to approximate the natural coagulation cascade with a single-step, additive-free preparation method. We investigated the effects of HAS on monolayer MSC cultures and in their natural niche, in 3D subchondral bone and marrow explants. Viability measurements, RT-qPCR evaluation for gene expression and flow cytometry for cell surface marker analysis were performed to compare the effects of FCS-, PRP-, or HAS-supplemented culture media. Monolayer MSCs showed significantly higher metabolic activity following 5 days’ incubation in HAS, and osteoblast-specific mRNA expression was markedly increased, while cells also retained their MSC-specific cell surface markers. A similar effect was observed on bone and marrow explants, which was further confirmed with confocal microscopy analysis. Moreover, markedly higher bone marrow preservation was observed with histology in case of HAS supplementation compared to FCS. These findings indicate possible application of HAS in regenerative solutions of skeletal diseases like OA or osteonecrosis.http://dx.doi.org/10.1155/2018/4854619
spellingShingle Melinda Simon
Bálint Major
Gabriella Vácz
Olga Kuten
István Hornyák
Adél Hinsenkamp
Dorottya Kardos
Marcell Bagó
Domonkos Cseh
Adrienn Sárközi
Denes Horvathy
Stefan Nehrer
Zsombor Lacza
The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
Stem Cells International
title The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
title_full The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
title_fullStr The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
title_full_unstemmed The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
title_short The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche
title_sort effects of hyperacute serum on the elements of the human subchondral bone marrow niche
url http://dx.doi.org/10.1155/2018/4854619
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