Induced pluripotent stem cells for cartilage repair: current status and future perspectives

Castro-Viñuelas, Rocío; Sanjurjo‐Rodríguez, Clara; Piñeiro-Ramil, María; Hermida‐Gómez, Tamara; Fuentes‐Boquete, Isaac; Toro, Javier de; Blanco, Francisco J.; Díaz‐Prado, Silvia

doi:10.22203/ecm.v036a08

Cited by 69 publications

(57 citation statements)

References 36 publications

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“…It has been proposed that these cells are intrinsically committed to bone formation through the endochondral ossification pathway, and that they follow this differentiation program after being exposed to chondrogenic stimuli [111]. However, the lack of reproducibility among chondrogenic protocols is also a feasible explanation [112], and it is important to note that good results have been obtained when performing chondrogenesis onto suitable scaffolds [95]. Finger et al (2003) found that immortalized cell lines obtained from chondrocytes were highly proliferative and showed less expression of genes involved in matrix synthesis and turnover than expected [113], in the same way that higher proliferation rates are related to reduced mineralization upon osteogenic induction [49,110].…”

Section: Chondrogenic Potentialmentioning

confidence: 99%

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

Piñeiro-Ramil

Sanjurjo‐Rodríguez

Castro-Viñuelas

et al. 2019

IJMS

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The unavailability of sufficient numbers of human primary cells is a major roadblock for in vitro repair of bone and/or cartilage, and for performing disease modelling experiments. Immortalized mesenchymal stromal cells (iMSCs) may be employed as a research tool for avoiding these problems. The purpose of this review was to revise the available literature on the characteristics of the iMSC lines, paying special attention to the maintenance of the phenotype of the primary cells from which they were derived, and whether they are effectively useful for in vitro disease modeling and cell therapy purposes. This review was performed by searching on Web of Science, Scopus, and PubMed databases from 1 January 2015 to 30 September 2019. The keywords used were ALL = (mesenchymal AND ("cell line" OR immortal*) AND (cartilage OR chondrogenesis OR bone OR osteogenesis) AND human). Only original research studies in which a human iMSC line was employed for osteogenesis or chondrogenesis experiments were included. After describing the success of the immortalization protocol, we focused on the iMSCs maintenance of the parental phenotype and multipotency. According to the literature revised, it seems that the maintenance of these characteristics is not guaranteed by immortalization, and that careful selection and validation of clones with particular characteristics is necessary for taking advantage of the full potential of iMSC to be employed in bone and cartilage-related research.

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Section: Chondrogenic Potentialmentioning

confidence: 99%

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

Piñeiro-Ramil

Sanjurjo‐Rodríguez

Castro-Viñuelas

et al. 2019

IJMS

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“…of allogeneic or autologous MSCs from pluripotent stem cells has emerged as a promising new strategy for stem cellbased therapy (Yang et al, 2017;Castro-Vinuelas et al, 2018;Soontararak et al, 2018;Yan et al, 2019). In the present study, we have derived MSCs from gene-corrected CS-iPSCs under a cGMP-compliant condition.…”

Section: Research Articlementioning

confidence: 99%

Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Wang

Min

et al. 2019

Protein Cell

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Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and

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“…Based on previous studies, we have developed a differentiation protocol 37,50 that mimics the development of pluripotent cells through the primitive streak mesendoderm-mesoderm intermediates-chondrocytes pathway. Additionally, the first step of EBs formation supposedly resembles the early post-implantation embryo and the cells in the EB should therefore be able to differentiate into all cell types 7 . Although more research is needed in order to optimise the current protocols for differentiating iPSCs into chondrocytes 7 , here we demonstrate that the iPSC-lines derived from patients with OA of the hand show less capacity to produce extracellular matrix rich in COL and PGs, after the differentiation process, in comparison to the iPSC-line derived from the healthy donor.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the first step of EBs formation supposedly resembles the early post-implantation embryo and the cells in the EB should therefore be able to differentiate into all cell types 7 . Although more research is needed in order to optimise the current protocols for differentiating iPSCs into chondrocytes 7 , here we demonstrate that the iPSC-lines derived from patients with OA of the hand show less capacity to produce extracellular matrix rich in COL and PGs, after the differentiation process, in comparison to the iPSC-line derived from the healthy donor. These preliminary results are in accordance with previous studies in which the extracellular matrix of chondrocytes derived from patients' iPSC resembled the one observed during advanced OA 11 .…”

Section: Discussionmentioning

confidence: 99%

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Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts

Castro-Viñuelas

Sanjurjo‐Rodríguez

Piñeiro-Ramil

et al. 2020

Sci Rep

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Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA. Osteoarthritis (OA) is a prevalent musculoskeletal disease that affects the joints, and it has a substantial effect on quality life 1-4. Hand OA affects predominantly the carpometacarpal joint (CMCJ), followed by the interphalangeal joints (IPJs), both proximal and distal 4. OA of the CMCJ, also known as rhizarthrosis or thumb OA, is the most common location in women over 55 years, and the severity is usually linked to handedness. Mechanical pain at the base of the thumb and the thenar eminence are the principal clinical manifestations of this pathology 5. Erosive hand OA is another form that may involve the CMCJ of the thumb as well as IPJs, in which central erosions are found in the subcondral bone 4. Although both the individual and the societal burden of hand OA are well known, knowledge and research results about its underlying cellular and molecular mechanisms are limited 3 , mainly due to the dearth of tissue samples and lack of animal models of this pathology 4,6. Cellular in vitro models are meaningful tools to shed light on the molecular mechanisms and pathways that are involved in hand OA. Primary chondrocytes, immortalized cell lines and mesenchymal stromal cells are commonly used as in vitro models of OA 6. However, they present

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Induced pluripotent stem cells for cartilage repair: current status and future perspectives

Cited by 69 publications

References 36 publications

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts

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