Tenogenically differentiated adipose-derived stem cells are effective in Achilles tendon repair in vivo

Norelli, Jolanta B; Plaza, Dawid P; Stal, Drew; Varghese, Anish; Liang, Haixiang; Grande, Daniel

doi:10.1177/2041731418811183

Cited by 41 publications

(47 citation statements)

References 60 publications

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“…During tissue repair, especially in bone, blood vessels supply not only oxygen and nutrients but also calcium and phosphate which are needed for mineralization [26]. us, for healing inflamed periapical lesions, the setting time of the materials applied in periapical lesion and consequent biological functions of MSCs during setting are important since the biological effects of the implanted materials in periapical lesions are contact time-dependent and extracts during setting influence MSCs' behaviors [9][10][11][12]. erefore, the effect of MTA against hMSCs was investigated in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…e setting time of the materials applied in periapical lesion of tooth and the consequent biological functions of MSCs during setting after implantation are important for the healing process of inflamed periapical lesions. Because the biological effects of the implanted materials are largely dependent on the contact time between materials and tissue, the ingredients and their amounts released from implant biomaterials give contact time dependent influence to MSCs' behaviors and biological functions [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Initial Cytotoxicity of Mineral Trioxide Aggregate (MTA) during Setting on Human Mesenchymal Stem Cells

Sooyoun

Lee

2019

Advances in Materials Science and Engineering

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Bone-marrow-derived human mesenchymal stem cells (hMSCs) which are important cell source for hard tissue regeneration stay near periapical lesions of tooth, playing an essential role in periodontal regeneration. Since the biomineralization process of MSCs is largely governed by the initial local environment, it is crucial to know the biological effects of dental bioceramic (mineral trioxide aggregate (MTA)) right after implantation. The purpose of this study was to evaluate the initial cytotoxicity of 4 different commercially available MTA materials (Endocem MTA, Ortho MTA, ProRoot MTA, and MTA Angelus) against hMSCs during or after setting using extracts of materials. The materials were mixed separately and placed into disk-shaped Teflon split molds (10 mm diameter and 2 mm thickness), and the sample discs were separated and eluted in the culture medium for 24 h. The extracts were exposed to hMSCs, and cytotoxicity was evaluated by the WST assay. In the present study, all 4 MTA products tested showed severe cytotoxicity at 100% and 50% extract, while 25% and 12.5% revealed 30∼100% depending on the MTA products. Endocem MTA showed severe cytotoxicity at 12.5% extract, while others showed relatively higher cell viability compared to Endocem MTA. Images of live and dead cells represented less live cells at 25% and 12.5%, confirming cell viability assay. Therefore, careful consideration of the concentration of MTA extracts is necessary, especially when applying MTA to the elderly patients to maintain the viability of hMSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Initial Cytotoxicity of Mineral Trioxide Aggregate (MTA) during Setting on Human Mesenchymal Stem Cells

Sooyoun

Lee

2019

Advances in Materials Science and Engineering

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“…Recent study found that tenocyte induced tenogenic differentiation of BMSCs by secreting exosomes containing Tgf- β 1 [ 12 ]. BMP-induced tenogenic differentiation of AMSCs enhanced the expression of collagen type I and scleraxis and exhibited improved histological score and collagen fiber dispersion range compared to undifferentiated AMSCs [ 13 ]. Although the induction capacities were low, insulin-like growth factor 1 and basic fibroblast growth factor could still promote BMSCs to differentiate into tenocytes by upregulating collagen type I/III and scleraxis [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits

Chen

Zhang

et al. 2020

Stem Cells International

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Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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“…Recent study found that tenocyte induced tenogenic differentiation of BMSCs by secreting exosomes containing Tgf-β1 [11]. BMP-induced tenogenic differentiation of AMSCs enhanced the expression of collagen type I and scleraxis and exhibited improved histological score and collagen fiber dispersion range compared to undifferentiated AMSCs [12]. Although the induction capacities were low, insulin-like growth factor 1 and basic fibroblast growth factor could still promote BMSCs to differentiate into tenocytes by upregulating collagen type I/III and scleraxis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

Chen¹,

Zhang²,

Gu³

et al. 2020

Preprint

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Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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Tenogenically differentiated adipose-derived stem cells are effective in Achilles tendon repair in vivo

Cited by 41 publications

References 60 publications

Initial Cytotoxicity of Mineral Trioxide Aggregate (MTA) during Setting on Human Mesenchymal Stem Cells

Initial Cytotoxicity of Mineral Trioxide Aggregate (MTA) during Setting on Human Mesenchymal Stem Cells

Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

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