scholarly journals Rejuvenated Stem/Progenitor Cells for Cartilage Repair Using the Pluripotent Stem Cell Technology

2021 ◽  
Vol 8 (4) ◽  
pp. 46
Author(s):  
Naoki Nakayama ◽  
Sudheer Ravuri ◽  
Johnny Huard
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Preclinical Research ◽  
Chondral Defects ◽  
Age Related ◽  
Repair Activity ◽  
Self Repair

It is widely accepted that chondral defects in articular cartilage of adult joints are never repaired spontaneously, which is considered to be one of the major causes of age-related degenerative joint disorders, such as osteoarthritis. Since mobilization of subchondral bone (marrow) cells and addition of chondrocytes or mesenchymal stromal cells into full-thickness defects show some degrees of repair, the lack of self-repair activity in adult articular cartilage can be attributed to lack of reparative cells in adult joints. In contrast, during a fetal or embryonic stage, joint articular cartilage has a scar-less repair activity, suggesting that embryonic joints may contain cells responsible for such activity, which can be chondrocytes, chondroprogenitors, or other cell types such as skeletal stem cells. In this respect, the tendency of pluripotent stem cells (PSCs) to give rise to cells of embryonic characteristics will provide opportunity, especially for humans, to obtain cells carrying similar cartilage self-repair activity. Making use of PSC-derived cells for cartilage repair is still in a basic or preclinical research phase. This review will provide brief overviews on how human PSCs have been used for cartilage repair studies.

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

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kangkang Zha ◽  
Xu Li ◽  
Zhen Yang ◽  
Guangzhao Tian ◽  
Zhiqiang Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Damage ◽  
Cartilage Regeneration ◽  
Great Promise ◽  
Traditional Treatment ◽  
Different Types ◽  
Selection Of

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

Effects of Aging and TGF-Beta 3 on Chondrocyte and Mesenchymal Stem Cell Matrix Formation

2010 ◽  
Author(s):  
Isaac E. Erickson ◽  
Steven C. van Veen ◽  
Swarnali Sengupta ◽  
Sydney R. Kestle ◽  
Jason A. Burdick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Chondrocytes ◽  
Cell Types ◽  
Matrix Proteins ◽  
Cell Type ◽  
Cell Matrix ◽  
Age Related ◽  
Cartilage Restoration ◽  
Effects Of Aging

Articular cartilage pathology is common in the aged population. Numerous studies have shown that aged chondrocytes (CHs) are inferior to juvenile CHs in their ability to proliferate and produce cartilage-specific extracellular matrix proteins, potentially limiting their use in tissue engineering applications for cartilage restoration [1,2]. Mesenchymal stem cells (MSCs) are an alternative cell type that can be expanded in vitro while maintaining their ability to differentiate into cell types comparable to articular chondrocytes. However, organismal aging also influences human MSC proliferation [3,4] and multi-potential differentiation [5], though for chondrogenesis these findings are mixed, with some suggesting that aged progenitor cells retain their chondrogenic capacity [6]. The objective of this study was to assess age related differences in donor-matched CH and MSC potential for chondrogenic repair. In addition, the effects of the chondrogenic growth factor TGF-β3 on CHs and MSCs were evaluated.

scholarly journals Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guillermo Bauza ◽  
Anna Pasto ◽  
Patrick Mcculloch ◽  
David Lintner ◽  
Ava Brozovich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Adipogenic Differentiation ◽  
3D Culture ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
3D Scaffold

Abstract Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.

Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair

2016 ◽  
Vol 16 (4) ◽  
pp. 535-557 ◽  
Author(s):  
Dimitris Reissis ◽  
Quen Oak Tang ◽  
Nina Catherine Cooper ◽  
Clare Francesca Carasco ◽  
Zakareya Gamie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Clinical Evidence ◽  
Articular Cartilage Repair

scholarly journals Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair

2016 ◽  
Vol 25 (21) ◽  
pp. 1659-1669 ◽  
Author(s):  
Paul Hindle ◽  
James Baily ◽  
Nusrat Khan ◽  
Leela C. Biant ◽  
A Hamish R. Simpson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Autologous Transplantation ◽  
Articular Cartilage Repair

Encouragement of Transplacental Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1202-1202
Author(s):  
Coy Heldermon ◽  
Mark Sands
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Cell Number ◽  
Dose Effect ◽  
High Dose ◽  
Cell Trafficking ◽  
Disease States ◽  
Mps Vii

Human fetomaternal cell trafficking has been demonstrated to result in persistent microchimerism of the mother and offspring from 20–100% of pregnancies. The level of microchimerism is small but in disease states may compose up to 0.96% of some cell types. This microchimersim could conceivably have therapeutic affects by serving as a reservoir of normally functioning stem cells. In order to determine if the level of microchimerism could be increased we have begun to explore methods to increase the number of stem cells and permeability of the placental barrier. To assess the affect of increasing stem cell number, granulocyte colony-stimulating factor (GCSF) was delivered subcutaneously during mid-gestation in pregnant heterozygous mucopolysaccharidosis VII (MPS VII, a deficiency of beta-glucuronidase) mice. We observed an increase in the proportion of sections from mutant offspring with demonstrable beta-glucuronidase producing cells from ∼2% in PBS treated mice to ∼25% in GCSF treated mice. To assess the affect of increasing placental permeability, pregnant MPS VII heterozygous mice were injected IV with vascular endothelial growth factor (VEGF) and a transfusion of 1 × 107 GFP positive bone marrow cells. We observed an increase in circulating GFP positive cells to 0.15% of circulating cells in 25% of the offspring of high dose VEGF-treated animals. Analysis of mutant offspring from the VEGF-treated animals reveals a dose effect of VEGF with 61% of sections from the group receiving the highest dose having demonstrable beta-glucuronidase producing cells. These studies demonstrate a proof-of-principle that microchimerism can be increased substantially and subsequent studies will focus on optimizing this transfer and analyzing therapeutic effect.

Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity

2017 ◽  
Vol 46 (10) ◽  
pp. 2540-2552 ◽  
Author(s):  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Ji Heon Rhim ◽  
Han-Jun Lee
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Cell Therapy ◽  
Cartilage Repair ◽  
Stem Cell Therapy ◽  
Peripheral Blood ◽  
Cell Populations

Background: Following successful preclinical studies, stem cell therapy is emerging as a candidate for the treatment of articular cartilage lesions. Because stem cell therapy for cartilage repair in humans is at an early phase, confusion and errors are found in the literature regarding use of the term stem cell therapy in this field. Purpose: To provide an overview of the outcomes of cartilage repair, elucidating the various cell populations used, and thus reduce confusion with regard to using the term stem cell therapy. Study Design: Systematic review. Methods: The authors systematically reviewed any studies on clinical application of mesenchymal stem cells (MSCs) in human subjects. A comprehensive search was performed in MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus for human studies that evaluated articular cartilage repair with cell populations containing MSCs. These studies were classified as using bone marrow–derived MSCs, adipose tissue–derived MSCs, peripheral blood–derived MSCs, synovium-derived MSCs, and umbilical cord blood–derived MSCs according to the entity of cell population used. Results: Forty-six clinical studies were identified to focus on cartilage repair with MSCs: 20 studies with bone marrow–derived MSCs, 21 studies with adipose tissue–derived MSCs, 3 studies with peripheral blood–derived MSCs, 1 study with synovium-derived MSCs, and 1 study with umbilical cord blood–derived MSCs. All clinical studies reported that cartilage treated with MSCs showed favorable clinical outcomes in terms of clinical scores or cartilage repair evaluated by MRI. However, most studies were limited to case reports and case series. Among these 46 clinical studies, 18 studies erroneously referred to adipose tissue–derived stromal vascular fractions as “adipose-derived MSCs,” 2 studies referred to peripheral blood–derived progenitor cells as “peripheral blood–derived MSCs,” and 1 study referred to bone marrow aspirate concentrate as “bone marrow–derived MSCs.” Conclusion: Limited evidence is available regarding clinical benefit of stem cell therapy for articular cartilage repair. Because the literature contains substantial errors in describing the therapeutic cells used, researchers need to be alert and observant of proper terms, especially regarding whether the cells used were stem cells or cell populations containing a small portion of stem cells, to prevent confusion in understanding the results of a given stem cell–based therapy.

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