Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering

Nakayama, Naoki; Pothiawala, Azim; Lee, John Y.; Matthias, Nadine; Umeda, Katsutsugu; Ang, Bryan; Huard, Johnny; Huang, Yun; Sun, Deqiang

doi:10.1007/s00018-019-03445-2

Cited by 32 publications

(33 citation statements)

References 209 publications

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“…Chondrocytes are the main cell type in articular cartilage (Archer & Francis-West, 2003), along with a scarce population of cartilage progenitor cells (CPCs) (Nakayama et al, 2020). The resident cells are embedded in a cartilage-speci c extracellular matrix (ECM) that consists of collagen type II, large aggregating proteoglycans (PGs; e.g.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

Matta

Lewis

Fellows

et al. 2020

Preprint

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Chondrogenic progenitor cells (CPCs) may be used as an alternative source of cells with potentially superior chondrogenic potential compared to mesenchymal stem cells (MSCs), and could be exploited for future regenerative therapies targeting articular cartilage in degenerative diseases such as osteoarthritis (OA). In this study, we hypothesised that CPCs derived from OA cartilage may be characterised by a distinct channelome. First, a global transcriptomic analysis using Affymetrix microarrays was performed. We studied the profiles of those ion channel and transporter families that may be relevant to chondroprogenitor cell physiology. Following validation of the microarray data, we examined the role of calcium-dependent potassium channels in CPCs and observed functional large conductance calcium-activated potassium channels (BK) involved in the maintenance of chondroprogenitor phenotype. In line with our very recent results, we found that the KCNMA1 gene was upregulated in CPCs and observed currents that could be attributed to the BK channel in both cell types. Through characterisation of their channelome we demonstrate that CPCs are a distinct cell population but are highly similar to MSCs in many respects. This work adds key mechanistic data to the in-depth characterisation of CPCs and their phenotype in the context of cartilage regeneration.

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Section: Introductionmentioning

confidence: 99%

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

Matta

Lewis

Fellows

et al. 2020

Preprint

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“…Research focusing on derivation of chondrocytes from iPSCs for cartilage regeneration has gained increasing attention in recent years, though it still remains challenging to obtain phenotypic articular chondrocytes ( 28 ). In this study, the phenotype, chondrogenic capability, and transcriptome of isogenic MC-Chs or NCC-Chs differentiated from blood-derived hiPSCs along the mesodermal and ectomesodermal lineage, respectively, were characterized.…”

Section: Discussionmentioning

confidence: 99%

Derivation of Isogenic Mesodermal and Ectomesodermal Chondrocytes from Human Induced Pluripotent Stem Cells for Articular Cartilage Regeneration

Lee

Stebbins

Jiao

et al. 2020

Preprint

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Generating phenotypic chondrocytes from human pluripotent stem cells through driving developmental lineage-specific differentiation remains to be of great interest in the field of cartilage regeneration. In this study, we derived chondrocytes from human induced pluripotent stem cells (hiPSCs) along the mesodermal or ectomesodermal lineages to prepare isogenic mesodermal cell-derived chondrocytes (MC-Chs) or neural crest cell-derived chondrocytes (NCC-Chs), respectively, and further evaluated differences in their cellular and molecular characteristics and cartilage repair capabilities. Our results showed that both lineage-derived chondrocytes expressed hyaline cartilage-associated markers and were capable of forming hyaline cartilage-like tissue ectopically and at joint defects. Moreover, NCC-Chs showed the absence of markers of hypertrophic chondrocytes and revealed a closer morphological resemblance to articular chondrocytes and a greater capability of producing glycosaminoglycans and collagen type 2 at cartilage defects compared to MC-Chs. It was found that the profile of global transcript expression of NCC-Chs more closely resembled that of native chondrocytes (NCs) than that of MC-Chs. Induced by additional growth factors identified through the analysis of transcriptome comparison to NCs, both MC-Chs and NCC-Chs showed a further increase in the phenotype of hyaline cartilage chondrocytes. Results of this study reveal differences in cellular and molecular characteristics and cartilage repair capabilities between isogenic hiPSC-derived MC-Chs and NCC-Chs and demonstrate that chondrocytes derived from hiPSCs along the ectomesodermal lineage are a potential cell source for articular cartilage regeneration.

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“…While drawing attention to the prevailing need to investigate novel methods for maximizing the clinical utility of MSCs is a focus of this review, a plurality of other therapeutic paradigms are under continual development and demonstrate tremendous potential for treating and/or modeling the complex, multifactorial conditions described herein. Following their discovery in the seminal works of Takahashi et al (2007), iPSCs have contributed to astounding advancements in personalized medicine, disease modeling, and cellular therapy; indeed, iPSCs have been used as model system and treatment paradigm for AD (Devineni et al, 2016;Tcw, 2019;Penney et al, 2020), RA (Cassotta et al, 2020), OA (Dubey et al, 2018;Nakayama et al, 2020); and OP (Paspaliaris and Kolios, 2019;Rana et al, 2019). iPSCs retain several theoretical advantages over MSCs when applied to cellular therapies: in addition to being capable of unrestrained growth, they demonstrate relatively minimal immunogenicity and can be differentiated into a wide gamut of specific cell niches.…”

Section: Alternative Treatment Paradigmsmentioning

confidence: 99%

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

Culibrk

Hahn

2020

Front. Aging Neurosci.

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Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.

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Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering

Cited by 32 publications

References 209 publications

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

Transcriptome-based screening of ion channels and transporters in a migratory chondroprogenitor cell line isolated from late-stage osteoarthritic cartilage

Derivation of Isogenic Mesodermal and Ectomesodermal Chondrocytes from Human Induced Pluripotent Stem Cells for Articular Cartilage Regeneration

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

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