Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

Zha, Kangkang; Li, Xu; Yang, Zhen; Tian, Guangzhao; Sun, Zhiqiang; Xiang, Sheng; Dai, Yongjing; Liu, Shuyun; Guo, Quanyi

doi:10.1038/s41536-021-00122-6

Cited by 114 publications

(96 citation statements)

References 183 publications

(101 reference statements)

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“…Additionally, MSC marker expression increases after culture expansion [23]. The inability to discriminate between cell populations based on immunophenotype is a known drawback in MSC research [35]. To verify the existence of a true and pure meniscus progenitor population, specific markers are currently lacking.…”

Section: Discussionmentioning

confidence: 99%

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Korpershoek

Rikkers

Windt

et al. 2021

IJMS

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Meniscus injuries can be highly debilitating and lead to knee osteoarthritis. Progenitor cells from the meniscus could be a superior cell type for meniscus repair and tissue-engineering. The purpose of this study is to characterize meniscus progenitor cells isolated by differential adhesion to fibronectin (FN-prog). Human osteoarthritic menisci were digested, and FN-prog were selected by differential adhesion to fibronectin. Multilineage differentiation, population doubling time, colony formation, and MSC surface markers were assessed in the FN-prog and the total meniscus population (Men). Colony formation was compared between outer and inner zone meniscus digest. Chondrogenic pellet cultures were performed for redifferentiation. FN-prog demonstrated multipotency. The outer zone FN-prog formed more colonies than the inner zone FN-prog. FN-prog displayed more colony formation and a higher proliferation rate than Men. FN-prog redifferentiated in pellet culture and mostly adhered to the MSC surface marker profile, except for HLA-DR receptor expression. This is the first study that demonstrates differential adhesion to fibronectin for the isolation of a progenitor-like population from the meniscus. The high proliferation rates and ability to form meniscus extracellular matrix upon redifferentiation, together with the broad availability of osteoarthritis meniscus tissue, make FN-prog a promising cell type for clinical translation in meniscus tissue-engineering.

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Section: Discussionmentioning

confidence: 99%

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Korpershoek

Rikkers

Windt

et al. 2021

IJMS

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“…While the field moves toward cell-free therapies ( 261 ) and mechanisms of action are mainly driven by paracrine and immunomodulatory effects ( 176 ), assessing the degree of commitment toward mesodermal linages to determine the most effective and suitable source for cell therapy may have less relevance. However, in other circumstances understanding how these differences affect the biology of MSCs could be an attractive avenue to study biological changes occurring throughout fetal development and adulthood ( 258 ), as well as to help define therapeutic strategies where use of MSCs is heavily influenced by such differentiation, such as bone and cartilage regeneration ( 262 , 263 ).…”

Section: Biological Properties Of Mscs Derived From Different Tissue Sourcesmentioning

confidence: 99%

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

2021

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Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.

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“…Bone marrow (BM-MSCs) and stem cells from adipose tissue (ATSCs) are the most commonly used sources of human adult MSCs (Brose et al, 2015). The capacity of MSCs to differentiate into chondrocytes varies, with synovial MSCs showing the most significant potential to differentiate into articular chondrocytes (Zha et al, 2021). For allogenenic mesenchymal stem cell therapy, the umbilical cord may be an appealing source.…”

Section: Cell Sources In Cartilage Tissue Engineeringmentioning

confidence: 99%

Nanocellulose-Based Scaffolds for Chondrogenic Differentiation and Expansion

Szustak

Gendaszewska‐Darmach

2021

Front. Bioeng. Biotechnol.

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Nanocellulose deserves special attention among the large group of biocompatible biomaterials. It exhibits good mechanical properties, which qualifies it for potential use as a scaffold imitating cartilage. However, the reconstruction of cartilage is a big challenge due to this tissue's limited regenerative capacity resulting from its lack of vascularization, innervations, and sparsely distributed chondrocytes. This feature restricts the infiltration of progenitor cells into damaged sites. Unfortunately, differentiated chondrocytes are challenging to obtain, and mesenchymal stem cells have become an alternative approach to promote chondrogenesis. Importantly, nanocellulose scaffolds induce the differentiation of stem cells into chondrocyte phenotypes. In this review, we present the recent progress of nanocellulose-based scaffolds promoting the development of cartilage tissue, especially within the emphasis on chondrogenic differentiation and expansion.

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Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

Cited by 114 publications

References 183 publications

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

Nanocellulose-Based Scaffolds for Chondrogenic Differentiation and Expansion

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