Mesenchymal Stem Cell Therapy in the Sports Knee

Dave, Lee Yee Han; Nyland, John; McKee, Paul B.; Caborn, David N.M.

doi:10.1177/1941738111427250

Cited by 7 publications

(4 citation statements)

References 100 publications

(169 reference statements)

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“…Several cell sources have been tested for meniscus healing, along with meniscus fibrochondrocytes, [20][21][22] chondrocytes, [23][24][25] MSCs, 26,27 synovium-derived stem cells, 28,29 infrapatellar fat pad (IPFP) progenitors, 28,30 and adipose-derived stem cells. [31][32][33] However, it has not yet been determined which cell type is ideal for repair.…”

Section: Introductionmentioning

confidence: 99%

Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources

Baek

Sovani

Choi

et al. 2018

Tissue Engineering Part A

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Hydrogel and electrospun scaffold materials support cell attachment and neotissue development and can be tuned to structurally and mechanically resemble native extracellular matrix by altering either electrospun fiber or hydrogel properties. In this study, we examined meniscus tissue generation from different human cell sources including meniscus cells derived from vascular and avascular regions, human bone marrow-derived mesenchymal stem cells, synovial cells, and cells from the infrapatellar fat pad (IPFP). All cells were seeded onto aligned electrospun collagen type I scaffolds and were optionally encapsulated in a tricomponent hydrogel. Single or multilayered constructs were generated and cultivated in defined medium with selected growth factors for 2 weeks. Cell viability, cell morphology, and gene-expression profiles were monitored using confocal microscopy, scanning electron microscopy, and quantitative polymerase chain reaction (qPCR), respectively. Multilayered constructs were examined with histology, immunohistochemistry, qPCR, and for tensile mechanical properties. For all cell types, TGFβ1 and TGFβ3 treatment increased COL1A1, COMP, Tenascin C (TNC), and Scleraxis (SCX) gene expression and deposition of collagen type I protein. IPFP cells generated meniscus-like tissues with higher meniscogenic gene expression, mechanical properties, and better cell distribution compared to other cell types studied. We show proof of concept that electrospun collagen scaffolds support neotissue formation and IPFP cells have potential for use in cell-based meniscus regeneration strategies.

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Section: Introductionmentioning

confidence: 99%

Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources

Baek

Sovani

Choi

et al. 2018

Tissue Engineering Part A

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“…Alternative cell sources have been assessed for their capacity to generate meniscus-like tissues. These include chondrocytes, 13,14 bone marrow-derived mesenchymal stem cells (BM-MSC), 15,16 synovium-derived stem cells, 17,18 infrapatellar fat pad progenitors, 17 and adipose-derived stem cells (ADSC) 19,20 have been tested. However, the target phenotype of a meniscogenic cell is poorly defined.…”

mentioning

confidence: 99%

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Grogan

Duffy

Pauli

et al. 2018

Journal Orthopaedic Research

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Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype. RNA was isolated from either the tissue directly or following cell isolation and 2 weeks in monolayer culture. RNA was hybridized on human genome arrays. Differentially expressed (DE) genes were identified by ranking analysis. DAVID pathway analysis was performed and visualized using STRING analysis. Quantitative PCR (qPCR) on additional donor menisci (tissues and cells) were used to validate array data. Avas cells cultured in 3D were subjected to qPCR to compare with the array-generated data. A total of 387 genes were DE based on differentiation state (>3-fold change; p < 0.01). In Avas-cultured cells, the upregulated pathways included focal adhesion, ECM-receptor interaction, regulation of actin cytoskeleton, and PDGF Signaling. In 3D-cultured Avas cells, TGFβ1 or combinations of TGFβ1 and BMP6 were most effective to promote an Avas tissue phenotype. THBS2 and THBS4 expression levels were identified as a means to denote meniscus cell phenotype status. We identified the key gene expression profiles, new markers and pathways involved in characterizing the Avas meniscus phenotype in the native state and during in vitro dedifferentiation and redifferentiation. These data served to screen 3D conditions to generate meniscus-like neotissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1947-1958, 2018.

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“…The most potent chondrogenic differentiation inducers are transforming growth factor β, bone morphogenic protein, fibroblast growth factor, and insulin-like growth factor 1 [25][26][27]. The induction process can be enhanced by steroids.…”

Section: Growth Factorsmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy in Cartilage Injuries of Knee – Review

Debnath¹

2020

Int J Orthop Sports Med

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Full-thickness cartilage injuries when left alone would increase the risk of osteoarthritis (OA) with severe associated pain and functional disability. The capability of the mesenchymal stem cells (MSCs) to repair and regenerate cartilage has been widely investigated. Articular cartilage defect may result from direct trauma or chronic degeneration. The subchondral bone plays an important role in healing through the presence of mesenchymal elements. MSCs are the most representative adult stem cells. It was observed that BM-MSCs (Bone Marrow derived MSCs) had superior chondrogenic differentiation capacity as compared to MSCs from other origins. It has been observed that a MSC density of 5 × 107 or 5 × 108 cells per milliliter embedded in a collagen gel had more proteoglycans than lower cell densities, better facilitating cartilage defect healing. The most potent chondrogenic differentiation inducers are transforming growth factor β, bone morphogenic protein, fibroblast growth factor, and insulin-like growth factor 1. Most commonly used delivery system for MSCs are either sealant or scaffold based. Ideal scaffold should have similar characteristics to the native tissue. The scaffold has the advantage of withstanding the in-vivo loading environment and protects the embedded cells. There is contradictory evidence regarding injectable treatment with BM-MSCs suggesting scaffolds may be required for the regeneration of cartilage. There is high quality of evidence to support MSC therapy but further refinement of methodology will be required to support its routine clinical use. There are few options to be explored e.g. MSC exosomes, genetic engineering and epigenetic regulatory mechanisms governing MSC biology

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Mesenchymal Stem Cell Therapy in the Sports Knee

Cited by 7 publications

References 100 publications

Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources

Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering

Mesenchymal Stem Cell Therapy in Cartilage Injuries of Knee – Review

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