scholarly journals Migratory chondroprogenitors retain superior intrinsic chondrogenic potential for regenerative cartilage repair as compared to human fibronectin derived chondroprogenitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elizabeth Vinod ◽  
Noel Naveen Johnson ◽  
Sanjay Kumar ◽  
Soosai Manickam Amirtham ◽  
Jithu Varghese James ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Culture Conditions ◽  
Adhesion Assay ◽  
Preclinical Research ◽  
Repair Tissue ◽  
Cell Based Therapy ◽  
Chondrogenic Potential ◽  
Cell Groups ◽  
Marker Profile

AbstractCell-based therapy for articular hyaline cartilage regeneration predominantly involves the use of mesenchymal stem cells and chondrocytes. However, the regenerated repair tissue is suboptimal due to the formation of mixed hyaline and fibrocartilage, resulting in inferior long-term functional outcomes. Current preclinical research points towards the potential use of cartilage-derived chondroprogenitors as a viable option for cartilage healing. Fibronectin adhesion assay-derived chondroprogenitors (FAA-CP) and migratory chondroprogenitors (MCP) exhibit features suitable for neocartilage formation but are isolated using distinct protocols. In order to assess superiority between the two cell groups, this study was the first attempt to compare human FAA-CPs with MCPs in normoxic and hypoxic culture conditions, investigating their growth characteristics, surface marker profile and trilineage potency. Their chondrogenic potential was assessed using mRNA expression for markers of chondrogenesis and hypertrophy, glycosaminoglycan content (GAG), and histological staining. MCPs displayed lower levels of hypertrophy markers (RUNX2 and COL1A1), with normoxia-MCP exhibiting significantly higher levels of chondrogenic markers (Aggrecan and COL2A1/COL1A1 ratio), thus showing superior potential towards cartilage repair. Upon chondrogenic induction, normoxia-MCPs also showed significantly higher levels of GAG/DNA with stronger staining. Focused research using MCPs is required as they can be suitable contenders for the generation of hyaline-like repair tissue.

scholarly journals Microfracture Versus Drilling of Articular Cartilage Defects: A Systematic Review of the Basic Science Evidence

2020 ◽  
Vol 8 (8) ◽  
pp. 232596712094531 ◽  
Author(s):  
Matthew J. Kraeutler ◽  
Gianna M. Aliberti ◽  
Anthony J. Scillia ◽  
Eric C. McCarty ◽  
Mary K. Mulcahey
Keyword(s):  
Systematic Review ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Basic Science ◽  
Science Studies ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Marrow Stimulation

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.

scholarly journals Synergistic Effects of FGF-18 and TGF-β3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Liangjie Huang ◽  
Lingxian Yi ◽  
Chunli Zhang ◽  
Ying He ◽  
Liangliang Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Positive Impact ◽  
Synergistic Effects ◽  
Cartilage Regeneration ◽  
Matrix Deposition ◽  
Cell Based Therapy ◽  
Chondrogenic Potential

Cell-based therapy serves as an effective way for cartilage repair. Compared with a limited source of autologous chondrocytes, adipose-derived stem cells (ADSCs) are proposed as an attractive cell source for cartilage regeneration. How to drive chondrogenic differentiation of ADSCs efficiently remains to be further investigated. TGF-β3 has shown a strong chondrogenic action on ADSCs. Recently, fibroblast growth factor 18 (FGF-18) has gained marked attention due to its anabolic effects on cartilage metabolism, but existing data regarding the role of FGF-18 on the chondrogenic potential of mesenchymal stem cells (MSCs) are conflicting. In addition, whether the combined application of FGF-18 and TGF-β3 would improve the efficiency of the chondrogenic potential of ADSCs has not been thoroughly studied. In the current study, we isolated human ADSCs and characterized the expression of their surface antigens. Also, we evaluated the chondrogenic potential of FGF-18 on ADSCs using an in vitro pellet model by measuring glycosaminoglycan (GAG) content, collagen level, histologic appearance, and expression of cartilage-related genes. We found that FGF-18, similarly to TGF-β3, had a positive impact on chondrogenic differentiation and matrix deposition when presented throughout the culture period. More importantly, we observed synergistic effects of FGF-18 and TGF-β3 on the chondrogenic differentiation of ADSCs in the in vitro pellet model. Our results provide critical information on the therapeutic use of ADSCs with the help of FGF-18 and TGF-β3 for cartilage regeneration.

scholarly journals Stem Cells and Gene Therapy for Cartilage Repair

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Umile Giuseppe Longo ◽  
Stefano Petrillo ◽  
Edoardo Franceschetti ◽  
Alessandra Berton ◽  
Nicola Maffulli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Treatment Strategies ◽  
Cartilage Regeneration ◽  
Biochemical Properties ◽  
Cartilage Defects ◽  
Type I ◽  
Repair Tissue

Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

scholarly journals Pondering the Potential of Hyaline Cartilage–Derived Chondroprogenitors for Tissue Regeneration: A Systematic Review

Cartilage ◽  
2020 ◽  
pp. 194760352095163
Author(s):  
Elizabeth Vinod ◽  
Roshni Parameswaran ◽  
Boopalan Ramasamy ◽  
Upasana Kachroo
Keyword(s):  
Systematic Review ◽  
Translational Research ◽  
Cartilage Repair ◽  
Animal Studies ◽  
Hyaline Cartilage ◽  
Adhesion Assay ◽  
Multiple Sources ◽  
Phenotypic Profile ◽  
Cell Based Therapy

Objective Chondroprogenitors have recently gained prominence due to promising results seen in in vitro and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage–derived chondroprogenitors, with regard to their isolation, culture, and outcome measures. Design As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting. Result Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow–derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay–derived progenitors, although a direct comparison between the two cell populations is warranted. Conclusion Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.

scholarly journals Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
John Garcia ◽  
Claire Mennan ◽  
Helen S. McCarthy ◽  
Sally Roberts ◽  
James B. Richardson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Subcutaneous Fat ◽  
Cell Types ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Cell Based Therapy ◽  
Chondrogenic Potential

Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes. We have confirmed that there is a chondrogenic potency hierarchy ranging across these cell types, with the most potent being chondrocytes, followed by FP-MSCs, BM-MSCs, and lastly SCF-MSCs. We have also examined gene expression and surface marker profiles in a predictive model to identify cells with enhanced chondrogenic potential. In doing so, we have shown that Sox-9, Alk-1, and Coll X expressions, as well as immunopositivity for CD49c and CD39, have predictive value for all of the cell types tested in indicating chondrogenic potency. The findings from this study have significant clinical implications for the refinement and development of novel cell-based cartilage repair strategies.

scholarly journals Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1999
Author(s):  
Jade Perry ◽  
Anke J. Roelofs ◽  
Claire Mennan ◽  
Helen S. McCarthy ◽  
Alison Richmond ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Cartilage Repair ◽  
Stromal Cells ◽  
Fluorescent Protein ◽  
Joint Surface ◽  
Human Umbilical Cord ◽  
Repair Tissue ◽  
Adult Mice ◽  
Chondral Defects ◽  
Repair Mechanisms

Human umbilical cord (hUC)- or bone marrow (hBM)-derived mesenchymal stromal cells (MSCs) were evaluated as an allogeneic source of cells for cartilage repair. We aimed to determine if they could enhance healing of chondral defects with or without the recruitment of endogenous cells. hMSCs were applied into a focal joint surface injury in knees of adult mice expressing tdTomato fluorescent protein in cells descending from Gdf5-expressing embryonic joint interzone cells. Three experimental groups were used: (i) hUC-MSCs, (ii) hBM-MSCs and (iii) PBS (vehicle) without cells. Cartilage repair was assessed after 8 weeks and tdTomato-expressing cells were detected by immunostaining. Plasma levels of pro-inflammatory mediators and other markers were measured by electrochemiluminescence. Both hUC-MSC (n = 14, p = 0.009) and hBM-MSC (n = 13, p = 0.006) treatment groups had significantly improved cartilage repair compared to controls (n = 18). While hMSCs were not detectable in the repair tissue at 8 weeks post-implantation, increased endogenous Gdf5-lineage cells were detected in repair tissue of hUC-MSC-treated mice. This xenogeneic study indicates that hMSCs enhance intrinsic cartilage repair mechanisms in mice. Hence, hMSCs, particularly the more proliferative hUC-MSCs, could represent an attractive allogeneic cell population for treating patients with chondral defects and perhaps prevent the onset and progression of osteoarthritis.

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 Intra-Articular Injection of Autologous Adipose-Derived Stromal Vascular Fractions for the Cartilage Repair of Grade 2 and 3 Knee Osteoarthritis: A Confirmatory Clinical Trial

2021 ◽  
Author(s):  
Yin Zhang ◽  
Qing Bi ◽  
Taihen Yu ◽  
Zheping Hong ◽  
Yu Tong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Knee Osteoarthritis ◽  
Cartilage Repair ◽  
Clinical Symptoms ◽  
Rapid Development ◽  
Cartilage Regeneration ◽  
Substantial Improvement ◽  
Clinical Trial Registry ◽  
Knee Oa ◽  
Grade 3

Abstract BackgroundCartilage defect remains one of the most important reasons for the rapid development of knee osteoarthritis (OA). Numerous reports have confirmed the safety and clinical efficacy of autologous adipose-derived stromal vascular fractions (SVF), which has recently been used clinically to treat patients with knee OA. However, there is still no consensus as to whether SVF can promote cartilage regeneration. Herein, we purposed to evaluate the effectiveness of SVF in cartilage regeneration by developing cartilage model based on the 3D-FS-SPGR sequence.MethodsPatients with Kellgren-Lawrence grade 2-3 knee OA were recruited in our research. Then, we monitored patients and subsequently scored symptoms using WOMAC, VAS, and range of motion (ROM) before treatment and at 1, 3, 6, and 12 months post-treatment. The WORMS and MOCART were recorded by magnetic resonance imaging. The cartilage model of the patient was established using the 3D-FS-SPGR sequence, while the relevant parameters of the model were counted at baseline, 6, and 12 months.ResultsWe enrolled 47 patients (53 knees) with knee OA in this study, of which 29 knees were classified as grade 2, while 24 were assigned grade 3. No treatment-related adverse event was observed in our study. Notably, WOMAC, VAS, and ROM showed a significant improvement at 12 months. We further found that the thickness, volume, and surface of the cartilage defect decreased, while the volume of healthy cartilage increased in all regions, particularly in the medial femoral and tibia condyle. Moreover, the scores of WORMS and MOCART revealed a substantial improvement of cartilage repair at 12 months. ConclusionsTaken together, this study shows that intra-articular injection of SVF into the knee markedly improved the clinical symptoms of patients without the occurrence of adverse events, thereby repairing the damaged articular cartilage through cartilage regeneration.Trial registrationRetrospectively registered. Chinses Clinical Trial Registry with identifier ChiCTR2100042930. Registered 28 January 2021.

scholarly journals Patofisiologi dan Tatalaksana Osteochondral Lesion of the Talus

2019 ◽  
Vol 1 (2) ◽  
pp. 45
Author(s):  
Maghrizal Roychan ◽  
Andre Triadi Desnantyo
Keyword(s):  
Ct Scan ◽  
Cartilage Repair ◽  
Osteochondral Lesion ◽  
Operative Therapy ◽  
Cartilage Regeneration ◽  
Osteochondral Lesions ◽  
X Rays ◽  
Talar Dome ◽  
Operative Techniques ◽  
Reduced Space

ABSTRAKPenyakit Osteochondral Lesion of the Talus (OLT) adalah kelainan pada tulang talus di lapisan subchondral yang berupa lesi osteochondral pada talar dome dengan konsekuensi abnormalitas pada tulang rawan sendi talar. Pasien biasanya datang berobat ke tenaga kesehatan dengan keluhan yang tidak spesifik dan dengan gejala seperti nyeri pada pergelangan kaki, bengkak serta berkurangnya berkurangnya ruang gerak. Penegakan diagnosis bisa dilakukan dengan anamnesis, pemeriksaan fisik dan pemeriksaan penunjang sederhana seperti foto X-ray maupun pemeriksaan penunjang canggih seperti CT-Scan dan MRI. Tatalaksana OLT bervariasi. Tatalaksana pada OLT tergantung dari tahapan lesi, kronisitasnya, dan keluhan simtomatis yang menyertainya. Pasien dengan keluhan simtomatis yang akut dan non-displaced sering diberikan terapi nonoperatif biasanya berupa terapi konservatif dengan imobilisasi. Lesi yang tidak berhasil atau tidak menunjukkan perbaikan dalam keluhan simtomatisnya setelah 3 sampai 6 bulan, serta lesi dengan displacement dapat direncanakan untuk terapi operatif. Ada beberapa macam tehnik operatif yang dapat dilakukan untuk menyembuhkan OLT. Tehnik operatif ini dapat dikategorikan menjadi cartilage repair, cartilage regeneration dan cartilage replacement techniques.Kata kunci: osteochondral lesion of the talus, patofisiologi, tatalaksanaABSTRACTOsteochondral Lesion of the Talus (OLT) is an abnormality in the talus bone in the subchondral layer in the form of osteochondral lesions in the talar dome with consequent abnormalities in the talar joint cartilage. Patients usually come to a health care provider with nonspecific complaints and with symptoms such as pain in the ankles, swelling and reduced space for movement. The diagnosis can be made with a history, physical examination and simple investigations such as X-rays and sophisticated investigations such as CT-Scan and MRI. The management of OLT varies. The management of OLT depends on the stage of the lesion, its chronicity, and the accompanying symptomatic complaints. Patients with acute and non-displaced symptomatic complaints are often given nonoperative therapy usually in the form of conservative therapy with immobilization. Lesions that are unsuccessful or show no improvement in symptomatic complaints after 3 to 6 months, and lesions with displacement can be planned for operative therapy. There are several types of operative techniques that can be done to cure OLT. These operative techniques can be categorized into cartilage repair, cartilage regeneration and cartilage replacement techniques. Keywords: osteochondral lesion of the talus, patophysiology, treatment

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.

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