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Thy as an expected adverse event. Keywords: CyclopamineMedChemExpress Cyclopamine Achilles tendon, Mesenchymal stromal cells, OsteogenesisBackground Tendon pathologies are a common problem especially in people of working age. The tendon healing process includes the formation of a hematoma, the local infiltration of inflammatory cells, the release of cytokines and growth factors followed by the?2014 Machova Urdzikova et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Machova Urdzikova et al. BioMedical Engineering OnLine 2014, 13:42 http://www.biomedical-engineering-online.com/content/13/1/Page 2 offormation of new extracellular matrix, new blood vessels and finally maturation and organization of the tendon tissue. Various cell-based therapies have been used to treat tendon pathologies in several in vivo studies [1-3] and at least one clinical trial (OrthADAPT; ClinicalTrials.gov identifier NCT01687777). Clinically relevant cellbased therapies often utilize adult stem cells, e.g. multipotent mesenchymal stromal cells. Mesenchymal stromal cells of various origins have been implanted directly into a tendon injury or attached to biodegradable scaffolds used to repair the tendon; they have shown an apparent beneficial effect on the healing process [4] and migrated to the injured tendon [5]. It was repeatedly shown that the delivery of mesenchymal stromal cells can create an optimal environment to support tendon tissue regeneration via the formation of extracellular matrix, enhanced vascularization, the production of supporting factors, modulation of the immunoresponse and the replacement of damaged cells [4,6]. Our aim was to describe the effect of the xenogeneic transplantation of human multipotent mesenchymal stromal cells (hMSCs) prepared under Good Manufacturing Practice (GMP) conditions on the healing process of rat Achilles tendons and also to identify potential side effects of human mesenchymal cells (tumorigenesis, wrong differentiation pathways) transplanted into a tendon injury to confirm the safety of hMSC treatment.MethodsCell isolation and cultivationhMSCs were isolated from the bone marrow of healthy human donors. All procedures for hMSC preparation were performed under GMP in the spin-off company Bioinova, Ltd. (Prague, Czech Republic) and approved by the State Institute for Drug Control of the Czech Republic (SUKL, Czech Republic). The mononuclear fraction containing hMSCs was separated from the bone marrow by gradient centrifugation using 25 Gelofusine (B. Braun, Melsungen, Germany) and seeded on plastic dishes at a concentration of 5 ?10 ?106 cells/75 cm2. The cells were expanded in media containing Alpha MEM Eagle without Deoxyribonucleotides, Ribonucleotides and UltraGlutamin (Lonza, Basel, Switzerland) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 supplemented with 5 mixed allogeneic Ro4402257 site thrombocyte lysate (Bioinova, Prague, Czech Republic) and 10 g/ml Gentamicin (Lek Pharmaceuticals, Ljublanja, Slovenia); non-adherent cells were washed out by changing the medium. When the cells reached 80 confluence, they were detached from the surface of the dishes using 1 ml/75 cm2 o.Thy as an expected adverse event. Keywords: Achilles tendon, Mesenchymal stromal cells, OsteogenesisBackground Tendon pathologies are a common problem especially in people of working age. The tendon healing process includes the formation of a hematoma, the local infiltration of inflammatory cells, the release of cytokines and growth factors followed by the?2014 Machova Urdzikova et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Machova Urdzikova et al. BioMedical Engineering OnLine 2014, 13:42 http://www.biomedical-engineering-online.com/content/13/1/Page 2 offormation of new extracellular matrix, new blood vessels and finally maturation and organization of the tendon tissue. Various cell-based therapies have been used to treat tendon pathologies in several in vivo studies [1-3] and at least one clinical trial (OrthADAPT; ClinicalTrials.gov identifier NCT01687777). Clinically relevant cellbased therapies often utilize adult stem cells, e.g. multipotent mesenchymal stromal cells. Mesenchymal stromal cells of various origins have been implanted directly into a tendon injury or attached to biodegradable scaffolds used to repair the tendon; they have shown an apparent beneficial effect on the healing process [4] and migrated to the injured tendon [5]. It was repeatedly shown that the delivery of mesenchymal stromal cells can create an optimal environment to support tendon tissue regeneration via the formation of extracellular matrix, enhanced vascularization, the production of supporting factors, modulation of the immunoresponse and the replacement of damaged cells [4,6]. Our aim was to describe the effect of the xenogeneic transplantation of human multipotent mesenchymal stromal cells (hMSCs) prepared under Good Manufacturing Practice (GMP) conditions on the healing process of rat Achilles tendons and also to identify potential side effects of human mesenchymal cells (tumorigenesis, wrong differentiation pathways) transplanted into a tendon injury to confirm the safety of hMSC treatment.MethodsCell isolation and cultivationhMSCs were isolated from the bone marrow of healthy human donors. All procedures for hMSC preparation were performed under GMP in the spin-off company Bioinova, Ltd. (Prague, Czech Republic) and approved by the State Institute for Drug Control of the Czech Republic (SUKL, Czech Republic). The mononuclear fraction containing hMSCs was separated from the bone marrow by gradient centrifugation using 25 Gelofusine (B. Braun, Melsungen, Germany) and seeded on plastic dishes at a concentration of 5 ?10 ?106 cells/75 cm2. The cells were expanded in media containing Alpha MEM Eagle without Deoxyribonucleotides, Ribonucleotides and UltraGlutamin (Lonza, Basel, Switzerland) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 supplemented with 5 mixed allogeneic thrombocyte lysate (Bioinova, Prague, Czech Republic) and 10 g/ml Gentamicin (Lek Pharmaceuticals, Ljublanja, Slovenia); non-adherent cells were washed out by changing the medium. When the cells reached 80 confluence, they were detached from the surface of the dishes using 1 ml/75 cm2 o.

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