Hypoxic culture conditions induce increased metabolic rate and collagen gene expression in ACL‐derived cells

Kowalski, Tomasz; Leong, Natalie L.; Dar, Ayelet; Wu, Ling; Kabir, Nima Mohseni; Khan, Adam Z.; Eliasberg, Claire D.; Pedron, Andrew; Karayan, Anthony; Lee, Siyoung; Treuheim, Theodor Di Pauli von; Jin, Jiacheng; Wu, Bian; Evseenko, Denis; McAllister, David R.; Petrigliano, Frank A.

doi:10.1002/jor.23116

Cited by 11 publications

(19 citation statements)

References 54 publications

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“…High donor variability for human BMSCs was demonstrated previously, suggesting that other patient-specific factors might influence the regenerative potential of MSCs to a greater extent than age25–27). The present study cannot isolate age effects and the effects of acute ACL-injury and knee osteoarthritis, as all young donors were subject to knee injury and all old donors received a total knee replacement due to osteoarthritis.…”

Section: Discussionmentioning

confidence: 78%

Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old Donors

Prager¹,

Kunz²,

Ebert³

et al. 2018

Knee Surg Relat Res

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PurposeMesenchymal stem cells (MSCs) isolated from the anterior cruciate ligament (ACL) share multiple characteristics of bone marrow-derived mesenchymal stem cells (BMSCs), allowing their use for regenerative therapies. Injuries to the ACL can affect people of all ages. This study assesses whether the regenerative potential of ACL-derived MSCs (ACL-MSCs) from old donors is as high as the potential of ACL-MSCs from young donors.Materials and MethodsACL-MSCs were isolated from ACL tissues obtained from young and old donors at the time of ACL reconstruction or arthroplasty. Proliferative capacity, multilineage differentiation potential (chondrogenic, osteogenic, and adipogenic lineages), and transcriptome-wide gene expression were assessed and compared between young and old donors. BMSCs of middle-aged donors served as an additional comparator.ResultsNo substantial differences between ACL-MSCs from young and old donors were observed in their proliferative capacity and multilineage differentiation potential. The latter did not substantially differ between both ACL-MSC groups and BMSCs. Differential expression of genes related to the cytoskeleton and to protein dephosphorylation amongst other pathways was detected between ACL-MSCs from young and old donors.ConclusionsRegenerative potential of ACL-MSCs from old donors was not substantially lower than that from young donors, suggesting that regenerative therapies of ACL tears are feasible in both age groups. In vivo studies of the effect of age on the efficacy of such therapies are needed.

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Section: Discussionmentioning

confidence: 78%

Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old Donors

Prager¹,

Kunz²,

Ebert³

et al. 2018

Knee Surg Relat Res

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“…Unlike other stem cell types, there is little research on the optimum culture conditions for LDSC survival and expansion. The survival and function of cells are normally dependent upon the culture conditions, and oxygen tension appears to have an effect on LDSC metabolism and matrix production [23]. In addition, certain media formulations and growth factors, such as basic fibroblast growth factor (bFGF) and transforming growth factor β 1 (TGF- β 1), promote stem cell proliferation and differentiation [24].…”

Section: Isolation and Culture Of Ldscsmentioning

confidence: 99%

“…Oxygen tension has been shown to increase metabolism and collagen expression of stem cells isolated from ACL [23]. …”

Section: The Ldsc Nichementioning

confidence: 99%

Ligament-Derived Stem Cells: Identification, Characterisation, and Therapeutic Application

Lee

Clegg

Comerford

et al. 2017

Stem Cells International

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Ligament is prone to injury and degeneration and has poor healing potential and, with currently ineffective treatment strategies, stem cell therapies may provide an exciting new treatment option. Ligament-derived stem cell (LDSC) populations have been isolated from a number of different ligament types with the majority of studies focussing on periodontal ligament. To date, only a few studies have investigated LDSC populations in other types of ligament, for example, intra-articular ligaments; however, this now appears to be a developing field. This literature review aims to summarise the current information on nondental LDSCs including in vitro characteristics of LDSCs and their therapeutic potential. The stem cell niche has been shown to be vital for stem cell survival and function in a number of different physiological systems; therefore, the LDSC niche may have an impact on LDSC phenotype. The role of the LDSC niche on LDSC viability and function will be discussed as well as the therapeutic potential of LDSC niche modulation.

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“…Hypoxia is the microenvironment of both tenocytes and MSCs. The oxygen tension has been shown to be 1-10% in tendon [16], 1-2% in bone marrow and approximately 3% in adipose tissue [17].…”

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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Hypoxic culture conditions induce increased metabolic rate and collagen gene expression in ACL‐derived cells

Cited by 11 publications

References 54 publications

Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old Donors

Mesenchymal Stem Cells Isolated from the Anterior Cruciate Ligament: Characterization and Comparison of Cells from Young and Old Donors

Ligament-Derived Stem Cells: Identification, Characterisation, and Therapeutic Application

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

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