Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes

ObjectiveArticular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.e., 1–5%) microenvironment. Human bone marrow mesenchymal stem cells (BM-MSC) exist physiologically within a similar range of oxygen tension. A low oxygen tension of 2% spontaneously induced chondrogenesis in micromass pellets of human BM-MSC. However, this is yet to be demonstrated in human IFP-MSC or other adipose tissue-sourced MSC. In this study, we explored the potential of low oxygen tension at 2% to drive the in vitro chondrogenesis of IFP-MSC. We hypothesized that 2% O2 will induce stable chondrogenesis in human IFP-MSC without the risk of undergoing endochondral ossification at ectopic sites of implantation.MethodsMicromass pellets of human IFP-MSC were cultured under 2% O2 or 21% O2 (normal atmosphere O2) in the presence or absence of chondrogenic medium with transforming growth factor-β3 (TGFβ3) for 3 weeks. Following in vitro chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.ResultsA low oxygen tension of 2% was unable to induce chondrogenesis in human IFP-MSC. In contrast, chondrogenic medium with TGFβ3 induced in vitro chondrogenesis. All pellets were devoid of any evidence of undergoing endochondral ossification after subcutaneous implantation in athymic mice.

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Co-culture of infrapatellar fat pad–derived mesenchymal stromal cells and articular chondrocytes in plasma clot for cartilage tissue engineering

Cytotherapy ◽

10.1016/j.jcyt.2017.04.003 ◽

2017 ◽

Vol 19 (7) ◽

pp. 881-894 ◽

Cited By ~ 12

Author(s):

Aditya Arora ◽

M. Sriram ◽

Anjaney Kothari ◽

Dhirendra S. Katti

Keyword(s):

Tissue Engineering ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Articular Chondrocytes ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Infrapatellar Fat Pad ◽

Fat Pad ◽

Plasma Clot

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Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy

Stem Cells International ◽

10.1155/2017/6843727 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Ronaldo J. F. C. do Amaral ◽

Henrique V. Almeida ◽

Daniel J. Kelly ◽

Fergal J. O’Brien ◽

Cathal J. Kearney

Keyword(s):

Stem Cells ◽

Articular Chondrocytes ◽

Donor Site ◽

Cartilage Regeneration ◽

Cell Types ◽

Donor Site Morbidity ◽

Infrapatellar Fat Pad ◽

Fat Pad ◽

Cell Sources

The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role onin vivocartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

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Phenotypic and functional properties of dedifferentiated fat cells derived from infrapatellar fat pad

Regenerative Therapy ◽

10.1016/j.reth.2021.12.006 ◽

2022 ◽

Vol 19 ◽

pp. 35-46

Author(s):

Koji Tanimoto ◽

Taro Matsumoto ◽

Yuki Nagaoka ◽

Tomohiko Kazama ◽

Chii Yamamoto ◽

...

Keyword(s):

Functional Properties ◽

Infrapatellar Fat Pad ◽

Fat Cells ◽

Fat Pad ◽

Dedifferentiated Fat Cells

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LC-MS-Based Metabolomics Analysis Revealed Deleterious Effect of Infrapatellar Fat Pad on Articular Chondrocytes of Osteoarthritis

10.21203/rs.3.rs-1199418/v1 ◽

2021 ◽

Author(s):

Ni Zeng ◽

Zhi-Peng Yan ◽

Tao Liao ◽

Jie-Ting Li ◽

Yan Chen ◽

...

Keyword(s):

Articular Chondrocytes ◽

Principal Component ◽

Tca Cycle ◽

Inhibitory Effect ◽

Glutamine Metabolism ◽

Infrapatellar Fat Pad ◽

Activity Levels ◽

Fat Pad ◽

Footprint Analysis ◽

Oa Chondrocytes

Abstract Objective: To investigate the interaction of infrapatellar fat pad/cartilage and related mechanisms in knee osteoarthritis (OA) using the metabolomics method.Method: Fat-conditioned media (FCM) of the infrapatellar fat pad from patients with OA were used to treat human OA chondrocytes. The extracellular metabolites of human OA chondrocytes were detected by nontargeted metabolic footprint analysis based on liquid chromatography and mass spectrometry (LC-MS). Then, the different metabolites were found, and the main metabolic pathways were explored, combined with bioinformatics methods.Results: After treatment with FCM for 48 h, the proliferation of human OA chondrocytes was slowed down, indicating that FCM had a certain inhibitory effect on the proliferation of human OA chondrocytes (P = 0.023). On the pattern diagram of principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA), after FCM treatment, the data sample areas were obviously separated, indicating that FCM can significantly affect the metabolic footprint of human OA chondrocytes. Through metabonomic identification, 131 different metabolites were screened after FCM treatment compared with before treatment. For 4 pathways in total, significantly different activity levels were discovered in pairwise comparisons: alanine, aspartate, and glutamate metabolism; citrate cycle (TCA cycle); arginine and proline metabolism; and phenylalanine metabolism.Conclusion: The infrapatellar fat pad aggravates OA chondrocyte injury and is involved in OA by disturbing the chondrocyte TCA cycle, amino acid metabolism, and glutamine metabolism, among others.

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The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02224-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yiqin Zhou ◽

Haobo Li ◽

Dong Xiang ◽

Jiahua Shao ◽

Qiwei Fu ◽

...

Keyword(s):

Clinical Efficacy ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Knee Arthroscopy ◽

Infrapatellar Fat Pad ◽

Control Group ◽

Knee Cartilage ◽

Fat Pad ◽

Group 12 ◽

Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

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